{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T23:41:48Z","timestamp":1792021308680,"version":"4.4.0"},"reference-count":209,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2021,1,25]],"date-time":"2021-01-25T00:00:00Z","timestamp":1611532800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005010","name":"Associazione Italiana per la Ricerca sul Cancro","doi-asserted-by":"publisher","award":["IG2016  ID:18464"],"award-info":[{"award-number":["IG2016  ID:18464"]}],"id":[{"id":"10.13039\/501100005010","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002428","name":"Austrian Science Fund","doi-asserted-by":"publisher","award":["T1112-B"],"award-info":[{"award-number":["T1112-B"]}],"id":[{"id":"10.13039\/501100002428","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Distant metastases are the main cause of cancer-related deaths in patients with advanced tumors. A standard diagnostic workup usually contains the identification of the tissue-of-origin of metastatic tumors, although under certain circumstances, it remains elusive. This disease setting is defined as cancer of unknown primary (CUP). Accounting for approximately 3\u20135% of all cancer diagnoses, CUPs are characterized by an aggressive clinical behavior and represent a real therapeutic challenge. The lack of determination of a tissue of origin precludes CUP patients from specific evidence-based therapeutic options or access to clinical trial, which significantly impacts their life expectancy. In the era of precision medicine, it is essential to characterize CUP molecular features, including the expression profile of non-coding RNAs, to improve our understanding of CUP biology and identify novel therapeutic strategies. This review article sheds light on this enigmatic disease by summarizing the current knowledge on CUPs focusing on recent discoveries and emerging diagnostic strategies.<\/jats:p>","DOI":"10.3390\/cancers13030451","type":"journal-article","created":{"date-parts":[[2021,1,25]],"date-time":"2021-01-25T12:28:31Z","timestamp":1611577711000},"page":"451","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":61,"title":["Cancer of Unknown Primary: Challenges and Progress in Clinical Management"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2737-4665","authenticated-orcid":false,"given":"Noemi","family":"Laprovitera","sequence":"first","affiliation":[{"name":"Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, 40126 Bologna, Italy"},{"name":"Department of Life Sciences and Biotechnologies, University of Ferrara, 44121 Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mattia","family":"Riefolo","sequence":"additional","affiliation":[{"name":"Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Ambrosini","sequence":"additional","affiliation":[{"name":"Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0195-8280","authenticated-orcid":false,"given":"Christiane","family":"Klec","sequence":"additional","affiliation":[{"name":"Division of Oncology, Medical University of Graz, 8036 Graz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8701-9462","authenticated-orcid":false,"given":"Martin","family":"Pichler","sequence":"additional","affiliation":[{"name":"Division of Oncology, Medical University of Graz, 8036 Graz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1595-6887","authenticated-orcid":false,"given":"Manuela","family":"Ferracin","sequence":"additional","affiliation":[{"name":"Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,1,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1559","DOI":"10.1126\/science.1203543","article-title":"A perspective on cancer cell metastasis","volume":"331","author":"Chaffer","year":"2011","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"v133","DOI":"10.1093\/annonc\/mdv305","article-title":"Cancers of unknown primary site: Esmo clinical practice guidelines for diagnosis, treatment and follow-up","volume":"26","author":"Fizazi","year":"2015","journal-title":"Ann. Oncol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1007\/s10549-008-9922-7","article-title":"Donor-derived breast cancer in a bone marrow transplantation recipient","volume":"113","author":"Golfinopoulos","year":"2009","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_4","unstructured":"NCCN (2020, January 31). Occult Primary (Version 2.2020). Available online: https:\/\/www.nccn.org\/professionals\/physician_gls\/pdf\/occult_blocks.pdf."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1038\/nrclinonc.2011.158","article-title":"Carcinomas of an unknown primary origin--diagnosis and treatment","volume":"8","author":"Massard","year":"2011","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.canep.2019.06.006","article-title":"The currently declining incidence of cancer of unknown primary","volume":"61","author":"Rassy","year":"2019","journal-title":"Cancer Epidemiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1056\/NEJMra1303917","article-title":"Cancer of unknown primary site","volume":"371","author":"Varadhachary","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2475","DOI":"10.1002\/ijc.28874","article-title":"Risk factors for cancers of unknown primary site: Results from the prospective epic cohort","volume":"135","author":"Kaaks","year":"2014","journal-title":"Int. J. Cancer"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1428","DOI":"10.1016\/S0140-6736(11)61178-1","article-title":"Cancer of unknown primary site","volume":"379","author":"Pavlidis","year":"2012","journal-title":"Lancet"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1318","DOI":"10.1038\/bjc.2013.386","article-title":"Cancer of unknown primary: A population-based analysis of temporal change and socioeconomic disparities","volume":"109","author":"Urban","year":"2013","journal-title":"Br. J. Cancer"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2720","DOI":"10.1093\/annonc\/mds063","article-title":"Cancer of unknown primary (cup): Does cause of death and family history implicate hidden phenotypically changed primaries?","volume":"23","author":"Hemminki","year":"2012","journal-title":"Ann. Oncol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1328","DOI":"10.1007\/s10147-019-01491-1","article-title":"Familial cancer of unknown primary","volume":"24","author":"Rassy","year":"2019","journal-title":"Int. J. Clin. Oncol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3700","DOI":"10.1002\/hed.25858","article-title":"Comprehensive management of hpv-related squamous cell carcinoma of the head and neck of unknown primary","volume":"41","author":"Rassy","year":"2019","journal-title":"Head Neck"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e13111","DOI":"10.1111\/eci.13111","article-title":"A new entity of abdominal squamous cell carcinoma of unknown primary","volume":"49","author":"Kattan","year":"2019","journal-title":"Eur. J. Clin. Investig."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1038\/s41416-018-0332-2","article-title":"Molecular characterisation and liquid biomarkers in carcinoma of unknown primary (cup): Taking the \u2018u\u2019 out of \u2018cup\u2019","volume":"120","author":"Conway","year":"2019","journal-title":"Br. J. Cancer"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2026","DOI":"10.1016\/j.ejca.2007.06.023","article-title":"Switching benchmarks in cancer of unknown primary: From autopsy to microarray","volume":"43","author":"Pentheroudakis","year":"2007","journal-title":"Eur. J. Cancer"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1530","DOI":"10.1136\/bmj.1.6177.1530","article-title":"Unknown primary adenocarcinoma: Incidence of overinvestigation and natural history","volume":"1","author":"Stewart","year":"1979","journal-title":"Br. Med. J."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1148\/radiology.134.2.7352215","article-title":"Diagnostic persistence in working up metastatic cancer with an unknown primary site","volume":"134","author":"Steckel","year":"1980","journal-title":"Radiology"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1002\/mpo.2950060404","article-title":"Adenocarcinoma of unknown primary site: A clinico-pathological study","volume":"6","author":"Snyder","year":"1979","journal-title":"Med. Pediatr. Oncol."},{"key":"ref_20","first-page":"53","article-title":"Metastatic and histologic presentations in unknown primary cancer","volume":"4","author":"Nystrom","year":"1977","journal-title":"Semin. Oncol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1097\/00000658-197711000-00014","article-title":"Metastatic carcinomas from occult primary tumors. A study of 254 patients","volume":"186","author":"Didolkar","year":"1977","journal-title":"Ann. Surg."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1177\/030089169307900507","article-title":"Neoplasms of unknown primary site: A clinicopathological study of autopsied patients","volume":"79","author":"Mayordomo","year":"1993","journal-title":"Tumori"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1097\/00000421-199302000-00007","article-title":"Cancer of unknown primary. A retrospective study based on 109 patients","volume":"16","author":"Maiche","year":"1993","journal-title":"Am. J. Clin. Oncol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1497","DOI":"10.1016\/0360-3016(87)90317-8","article-title":"Acups (adenocarcinoma of unknown primary site): A clinical and cost benefit analysis","volume":"13","author":"Hamilton","year":"1987","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1111\/j.1600-0463.2003.apm1111203.x","article-title":"Cancer of unknown primary: Clinicopathologic correlations","volume":"111","author":"Blaszyk","year":"2003","journal-title":"APMIS"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.anndiagpath.2004.12.003","article-title":"The value of postmortem examination in cases of metastasis of unknown origin-20-year retrospective data from a tertiary care center","volume":"9","author":"Ross","year":"2005","journal-title":"Ann. Diagn. Pathol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2035","DOI":"10.1001\/archinte.1988.00380090101024","article-title":"Early metastatic cancer of unknown primary origin at presentation. A clinical study of 302 consecutive autopsied patients","volume":"148","author":"Cvitkovic","year":"1988","journal-title":"Arch. Intern. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1002\/1097-0142(19850215)55:4<857::AID-CNCR2820550425>3.0.CO;2-Z","article-title":"Adenocarcinoma of unknown primary site. The brooke army medical center experience","volume":"55","author":"Jordan","year":"1985","journal-title":"Cancer"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1053\/j.seminoncol.2008.10.009","article-title":"Pathologic evaluation of unknown primary cancer","volume":"36","author":"Oien","year":"2009","journal-title":"Semin. Oncol."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Ramskold, D., Wang, E.T., Burge, C.B., and Sandberg, R. (2009). An abundance of ubiquitously expressed genes revealed by tissue transcriptome sequence data. PLoS Comput. Biol., 5.","DOI":"10.1371\/journal.pcbi.1000598"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Gevaert, O., Daemen, A., De Moor, B., and Libbrecht, L. (2009). A taxonomy of epithelial human cancer and their metastases. BMC Med. Genom., 2.","DOI":"10.1186\/1755-8794-2-69"},{"key":"ref_32","first-page":"99","article-title":"Coordinate expression of cytokeratins 7 and 20 define unique subsets of carcinoma","volume":"3","author":"Wang","year":"1995","journal-title":"Appl. Immunohistochem. Mol. Morphol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"962","DOI":"10.1038\/modpathol.3880175","article-title":"Cytokeratin 7 and cytokeratin 20 expression in epithelial neoplasms: A survey of 435 cases","volume":"13","author":"Chu","year":"2000","journal-title":"Mod. Pathol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1083\/jcb.200603161","article-title":"New consensus nomenclature for mammalian keratins","volume":"174","author":"Schweizer","year":"2006","journal-title":"J. Cell Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1196","DOI":"10.5858\/2000-124-1196-EOCAIC","article-title":"Expression of cytokeratins 7 and 20 in carcinomas of the extrahepatic biliary tract, pancreas, and gallbladder","volume":"124","author":"Duval","year":"2000","journal-title":"Arch. Pathol. Lab. Med."},{"key":"ref_36","first-page":"2840","article-title":"Characterization of cytokeratin 20 expression in pancreatic and colorectal cancer","volume":"5","author":"Wildi","year":"1999","journal-title":"Clin. Cancer Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1046\/j.1365-2559.2000.00932.x","article-title":"Cytokeratin profile relates to histological subtypes and intrahepatic location of intrahepatic cholangiocarcinoma and primary sites of metastatic adenocarcinoma of liver","volume":"37","author":"Shimonishi","year":"2000","journal-title":"Histopathology"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/S0925-4439(01)00056-4","article-title":"Cdx-1 and cdx-2 are expressed in human colonic mucosa and are down-regulated in patients with hirschsprung\u2019s disease associated enterocolitis","volume":"1537","author":"Lui","year":"2001","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1053\/gast.2000.18142","article-title":"Cdx1 and cdx2 expression during intestinal development","volume":"119","author":"Silberg","year":"2000","journal-title":"Gastroenterology"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2239","DOI":"10.1016\/S0002-9440(10)63074-X","article-title":"Loss of cdx2 expression and microsatellite instability are prominent features of large cell minimally differentiated carcinomas of the colon","volume":"159","author":"Hinoi","year":"2001","journal-title":"Am. J. Pathol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1097\/01.pas.0000131531.75602.b9","article-title":"Cdx-2 homeobox gene product expression in neuroendocrine tumors: Its role as a marker of intestinal neuroendocrine tumors","volume":"28","author":"Barbareschi","year":"2004","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1097\/01.pai.0000210416.53493.0f","article-title":"Diagnostic value of cdx-2 and ttf-1 expressions in separating metastatic neuroendocrine neoplasms of unknown origin","volume":"15","author":"Lin","year":"2007","journal-title":"Appl. Immunohistochem. Mol. Morphol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1097\/00000478-200303000-00003","article-title":"Cdx2, a highly sensitive and specific marker of adenocarcinomas of intestinal origin: An immunohistochemical survey of 476 primary and metastatic carcinomas","volume":"27","author":"Werling","year":"2003","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1385\/EP:15:3:247","article-title":"Cdx2 as a marker for neuroendocrine tumors of unknown primary sites","volume":"15","author":"Erickson","year":"2004","journal-title":"Endocr. Pathol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1309\/UKN6PVRKXHG422DA","article-title":"Usefulness of cdx2 and ttf-1 in differentiating gastrointestinal from pulmonary carcinoids","volume":"123","author":"Saqi","year":"2005","journal-title":"Am. J. Clin. Pathol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1097\/00129039-200503000-00009","article-title":"Cdx2 immunostaining as a gastrointestinal marker: Expression in lung carcinomas is a potential pitfall","volume":"13","author":"Mazziotta","year":"2005","journal-title":"Appl. Immunohistochem. Mol. Morphol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"643","DOI":"10.3346\/jkms.2005.20.4.643","article-title":"The usefulness of cdx-2 for differentiating primary and metastatic ovarian carcinoma: An immunohistochemical study using a tissue microarray","volume":"20","author":"Kim","year":"2005","journal-title":"J. Korean Med. Sci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1038\/modpathol.3800510","article-title":"Immunohistochemistry for estrogen and progesterone receptors in the distinction of primary and metastatic mucinous tumors in the ovary: An analysis of 124 cases","volume":"19","author":"Vang","year":"2006","journal-title":"Mod. Pathol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.1038\/modpathol.3800407","article-title":"Value of cdx2, villin, and alpha-methylacyl coenzyme a racemase immunostains in the distinction between primary adenocarcinoma of the bladder and secondary colorectal adenocarcinoma","volume":"18","author":"Suh","year":"2005","journal-title":"Mod. Pathol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"932","DOI":"10.1136\/jcp.2004.016964","article-title":"Expression pattern of ck7, ck20, cdx-2, and villin in intestinal-type sinonasal adenocarcinoma","volume":"57","author":"Kennedy","year":"2004","journal-title":"J. Clin. Pathol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"884","DOI":"10.1309\/9W8D3XCVLRA3858A","article-title":"Ttf-1, cytokeratin 7, 34betae12, and cd56\/ncam immunostaining in the subclassification of large cell carcinomas of the lung","volume":"122","author":"Rossi","year":"2004","journal-title":"Am. J. Clin. Pathol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1834","DOI":"10.1038\/s41379-019-0302-0","article-title":"A combination of the immunohistochemical markers ck7 and satb2 is highly sensitive and specific for distinguishing primary ovarian mucinous tumors from colorectal and appendiceal metastases","volume":"32","author":"Meagher","year":"2019","journal-title":"Mod. Pathol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1097\/PAI.0000000000000237","article-title":"Comparative sensitivities and specificities of antibodies to breast markers gcdfp-15, mammaglobin a, and different clones of antibodies to gata-3: A study of 338 tumors using whole sections","volume":"24","author":"Kandalaft","year":"2016","journal-title":"Appl. Immunohistochem. Mol. Morphol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1309\/AJCP0Q9UQTEESLHN","article-title":"Immunohistochemical evaluation of gata-3 expression in er-negative breast carcinomas","volume":"141","author":"Liu","year":"2014","journal-title":"Am. J. Clin. Pathol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.1016\/j.humpath.2012.11.003","article-title":"Gata3 expression in breast carcinoma: Utility in triple-negative, sarcomatoid, and metastatic carcinomas","volume":"44","author":"Subhawong","year":"2013","journal-title":"Hum. Pathol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1309\/AJCP5UAFMSA9ZQBZ","article-title":"Immunohistochemical evaluation of gata3 expression in tumors and normal tissues: A useful immunomarker for breast and urothelial carcinomas","volume":"138","author":"Liu","year":"2012","journal-title":"Am. J. Clin. Pathol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1038\/modpathol.2010.38","article-title":"A study of immunohistochemical differential expression in pulmonary and mammary carcinomas","volume":"23","author":"Yang","year":"2010","journal-title":"Mod. Pathol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1097\/PAS.0b013e3182a0218f","article-title":"Gata3: A multispecific but potentially useful marker in surgical pathology: A systematic analysis of 2500 epithelial and nonepithelial tumors","volume":"38","author":"Miettinen","year":"2014","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2156","DOI":"10.1002\/1097-0142(19890601)63:11<2156::AID-CNCR2820631115>3.0.CO;2-B","article-title":"Expression of gcdfp-15 in breast carcinomas. Relationship to pathologic and clinical factors","volume":"63","author":"Mazoujian","year":"1989","journal-title":"Cancer"},{"key":"ref_60","first-page":"105","article-title":"Immunohistochemistry of a gross cystic disease fluid protein (gcdfp-15) of the breast. A marker of apocrine epithelium and breast carcinomas with apocrine features","volume":"110","author":"Mazoujian","year":"1983","journal-title":"Am. J. Pathol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1111\/his.12645","article-title":"Gata-binding protein 3 enhances the utility of gross cystic disease fluid protein-15 and mammaglobin a in triple-negative breast cancer by immunohistochemistry","volume":"67","author":"Huo","year":"2015","journal-title":"Histopathology"},{"key":"ref_62","first-page":"860","article-title":"Mammaglobin, a mammary-specific member of the uteroglobin gene family, is overexpressed in human breast cancer","volume":"56","author":"Watson","year":"1996","journal-title":"Cancer Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1242\/dev.113.4.1093","article-title":"The transcription factor ttf-1 is expressed at the onset of thyroid and lung morphogenesis and in restricted regions of the foetal brain","volume":"113","author":"Lazzaro","year":"1991","journal-title":"Development"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1309\/550P-QLJX-D84W-F6DN","article-title":"Mucinous and nonmucinous bronchioloalveolar adenocarcinomas have distinct staining patterns with thyroid transcription factor and cytokeratin 20 antibodies","volume":"116","author":"Goldstein","year":"2001","journal-title":"Am. J. Clin. Pathol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1097\/PAS.0b013e31828ff59d","article-title":"Neuroendocrine carcinoma of the stomach: Morphologic and immunohistochemical characteristics and prognosis","volume":"37","author":"Ishida","year":"2013","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1097\/PGP.0b013e3181804bc6","article-title":"Ttf-1 expression in ovarian and uterine epithelial neoplasia and its potential significance, an immunohistochemical assessment with multiple monoclonal antibodies and different secondary detection systems","volume":"28","author":"Zhang","year":"2009","journal-title":"Int. J. Gynecol. Pathol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1111\/j.1365-2559.2006.02365.x","article-title":"Ttf-1 expression in primary ovarian epithelial neoplasia","volume":"48","author":"Graham","year":"2006","journal-title":"Histopathology"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1038\/modpathol.2008.4","article-title":"Thyroid transcription factor-1 expression in ovarian epithelial neoplasms","volume":"21","author":"Kubba","year":"2008","journal-title":"Mod. Pathol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1759","DOI":"10.1097\/PAS.0b013e3181131e21","article-title":"Thyroid transcription factor-1 expression in endometrial and endocervical adenocarcinomas","volume":"31","author":"Siami","year":"2007","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.1038\/modpathol.3800422","article-title":"Variable sensitivity and specificity of ttf-1 antibodies in lung metastatic adenocarcinoma of colorectal origin","volume":"18","author":"Comperat","year":"2005","journal-title":"Mod. Pathol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1136\/jcp.2005.030064","article-title":"Positive immunostaining for thyroid transcription factor-1 in primary and metastatic colonic adenocarcinoma: A note of caution","volume":"59","author":"Penman","year":"2006","journal-title":"J. Clin. Pathol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1881","DOI":"10.1097\/PAS.0b013e3181f884e8","article-title":"Thyroid transcription factor-1 expression in breast carcinomas","volume":"34","author":"Robens","year":"2010","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"718","DOI":"10.1016\/j.humpath.2005.04.007","article-title":"Thyroid transcription factor 1 expression in small cell carcinoma of the urinary bladder: An immunohistochemical profile of 44 cases","volume":"36","author":"Jones","year":"2005","journal-title":"Hum. Pathol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1038\/modpathol.3880044","article-title":"Thyroid transcription factor-1 is expressed in extrapulmonary small cell carcinomas but not in other extrapulmonary neuroendocrine tumors","volume":"13","author":"Agoff","year":"2000","journal-title":"Mod. Pathol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1046\/j.1365-2559.2000.00890.x","article-title":"Expression of thyroid transcription factor-1 in pulmonary and extrapulmonary small cell carcinomas and other neuroendocrine carcinomas of various primary sites","volume":"36","author":"Kaufmann","year":"2000","journal-title":"Histopathology"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.1097\/00000478-200009000-00004","article-title":"Value of thyroid transcription factor-1 immunostaining in distinguishing small cell lung carcinomas from other small cell carcinomas","volume":"24","author":"Ordonez","year":"2000","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1136\/jcp.54.9.727","article-title":"Merkel cell carcinoma can be distinguished from metastatic small cell carcinoma using antibodies to cytokeratin 20 and thyroid transcription factor 1","volume":"54","author":"Leech","year":"2001","journal-title":"J. Clin. Pathol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1097\/01.dad.0000183701.67366.c7","article-title":"Immunohistochemical distinction between merkel cell carcinoma and small cell carcinoma of the lung","volume":"28","author":"Bobos","year":"2006","journal-title":"Am. J. Dermatopathol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1097\/PAI.0b013e318205b059","article-title":"Combination of napsin a and ttf-1 immunohistochemistry helps in differentiating primary lung adenocarcinoma from metastatic carcinoma in the lung","volume":"19","author":"Ye","year":"2011","journal-title":"Appl. Immunohistochem. Mol. Morphol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1097\/PAI.0b013e3182612643","article-title":"Applications and limitations of immunohistochemical expression of \u201cnapsin-a\u201d in distinguishing lung adenocarcinoma from adenocarcinomas of other organs","volume":"21","author":"Kadivar","year":"2013","journal-title":"Appl. Immunohistochem. Mol. Morphol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.humpath.2009.06.014","article-title":"Napsin a and thyroid transcription factor-1 expression in carcinomas of the lung, breast, pancreas, colon, kidney, thyroid, and malignant mesothelioma","volume":"41","author":"Bishop","year":"2010","journal-title":"Hum. Pathol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1309\/AJCP8WO2EOIAHSOF","article-title":"The lung-restricted marker napsin a is highly expressed in clear cell carcinomas of the ovary","volume":"142","author":"Kandalaft","year":"2014","journal-title":"Am. J. Clin. Pathol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1038\/modpathol.3801002","article-title":"Diagnostic utility of thyroid transcription factors pax8 and ttf-2 (foxe1) in thyroid epithelial neoplasms","volume":"21","author":"Nonaka","year":"2008","journal-title":"Mod. Pathol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/j.ygyno.2006.08.052","article-title":"Emerging roles for pax8 in ovarian cancer and endosalpingeal development","volume":"104","author":"Bowen","year":"2007","journal-title":"Gynecol. Oncol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1097\/PAS.0b013e318216c112","article-title":"A comprehensive analysis of pax8 expression in human epithelial tumors","volume":"35","author":"Laury","year":"2011","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1053\/j.seminoncol.2008.10.006","article-title":"Treatment for patients with unknown primary cancer and favorable prognostic factors","volume":"36","author":"Hainsworth","year":"2009","journal-title":"Semin. Oncol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1053\/j.seminoncol.2008.10.005","article-title":"Treatment for patients with unknown primary carcinoma and unfavorable prognostic factors","volume":"36","author":"Greco","year":"2009","journal-title":"Semin. Oncol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"4679","DOI":"10.1200\/JCO.2002.04.019","article-title":"Development and validation of a prognostic model to predict the length of survival in patients with carcinomas of an unknown primary site","volume":"20","author":"Culine","year":"2002","journal-title":"J. Clin. Oncol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"e000502","DOI":"10.1136\/esmoopen-2019-000502","article-title":"How i treat cancers of unknown primary","volume":"4","author":"Zarkavelis","year":"2019","journal-title":"ESMO Open"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1016\/j.ctrv.2009.05.005","article-title":"Comparative survival with diverse chemotherapy regimens for cancer of unknown primary site: Multiple-treatments meta-analysis","volume":"35","author":"Golfinopoulos","year":"2009","journal-title":"Cancer Treat. Rev."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"2376","DOI":"10.1038\/bjc.1998.395","article-title":"A multicentre phase ii study of carboplatin and prolonged oral etoposide in the treatment of cancer of unknown primary site (cups)","volume":"77","author":"Warner","year":"1998","journal-title":"Br. J. Cancer"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1148","DOI":"10.1080\/02841860701843043","article-title":"Docetaxel and carboplatin combination chemotherapy as outpatient palliative therapy in carcinoma of unknown primary: A multicentre hellenic cooperative oncology group phase ii study","volume":"47","author":"Pentheroudakis","year":"2008","journal-title":"Acta Oncol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1007\/s00280-007-0604-7","article-title":"Multicenter phase-ii trial of irinotecan plus oxaliplatin [irox regimen] in patients with poor-prognosis cancer of unknown primary: A hellenic cooperative oncology group study","volume":"62","author":"Briasoulis","year":"2008","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1038\/sj.bjc.6604818","article-title":"Paclitaxel and carboplatin vs gemcitabine and vinorelbine in patients with adeno- or undifferentiated carcinoma of unknown primary: A randomised prospective phase ii trial","volume":"100","author":"Huebner","year":"2009","journal-title":"Br. J. Cancer"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1654","DOI":"10.1002\/cncr.29229","article-title":"Paclitaxel\/carboplatin with or without belinostat as empiric first-line treatment for patients with carcinoma of unknown primary site: A randomized, phase 2 trial","volume":"121","author":"Hainsworth","year":"2015","journal-title":"Cancer"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1016\/j.ejca.2012.01.011","article-title":"Cisplatin alone or combined with gemcitabine in carcinomas of unknown primary: Results of the randomised gefcapi 02 trial","volume":"48","author":"Fourcade","year":"2012","journal-title":"Eur. J. Cancer"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1007\/s12094-017-1807-y","article-title":"Seom clinical guideline on unknown primary cancer (2017)","volume":"20","author":"Losa","year":"2018","journal-title":"Clin. Transl. Oncol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"15149","DOI":"10.1073\/pnas.211566398","article-title":"Multiclass cancer diagnosis using tumor gene expression signatures","volume":"98","author":"Ramaswamy","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1126\/science.286.5439.531","article-title":"Molecular classification of cancer: Class discovery and class prediction by gene expression monitoring","volume":"286","author":"Golub","year":"1999","journal-title":"Science"},{"key":"ref_100","first-page":"7388","article-title":"Molecular classification of human carcinomas by use of gene expression signatures","volume":"61","author":"Su","year":"2001","journal-title":"Cancer Res."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"2503","DOI":"10.1200\/JCO.2008.17.9762","article-title":"Multicenter validation of a 1,550-gene expression profile for identification of tumor tissue of origin","volume":"27","author":"Monzon","year":"2009","journal-title":"J. Clin. Oncol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.jmoldx.2010.11.001","article-title":"Validation and reproducibility of a microarray-based gene expression test for tumor identification in formalin-fixed, paraffin-embedded specimens","volume":"13","author":"Pillai","year":"2011","journal-title":"J. Mol. Diagn."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"67","DOI":"10.2353\/jmoldx.2008.070099","article-title":"Interlaboratory performance of a microarray-based gene expression test to determine tissue of origin in poorly differentiated and undifferentiated cancers","volume":"10","author":"Dumur","year":"2008","journal-title":"J. Mol. Diagn."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.1097\/PAS.0b013e31828309c4","article-title":"A multicenter study directly comparing the diagnostic accuracy of gene expression profiling and immunohistochemistry for primary site identification in metastatic tumors","volume":"37","author":"Handorf","year":"2013","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/1746-1596-5-3","article-title":"Identification of tissue of origin in carcinoma of unknown primary with a microarray-based gene expression test","volume":"5","author":"Monzon","year":"2010","journal-title":"Diagn. Pathol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"4435","DOI":"10.1200\/JCO.2007.14.6969","article-title":"Gene expression profiling to identify the histogenetic origin of metastatic adenocarcinomas of unknown primary","volume":"26","author":"Horlings","year":"2008","journal-title":"J. Clin. Oncol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1093\/annonc\/mdv543","article-title":"Gene expression profiling identifies responsive patients with cancer of unknown primary treated with carboplatin, paclitaxel, and everolimus: Ncctg n0871 (alliance)","volume":"27","author":"Yoon","year":"2016","journal-title":"Ann. Oncol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1097\/PAT.0000000000000194","article-title":"Development and validation of a gene expression tumour classifier for cancer of unknown primary","volume":"47","author":"Tothill","year":"2015","journal-title":"Pathology"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"465","DOI":"10.5858\/2006-130-465-MCOHCU","article-title":"Molecular classification of human cancers using a 92-gene real-time quantitative polymerase chain reaction assay","volume":"130","author":"Ma","year":"2006","journal-title":"Arch. Pathol. Lab. Med."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"3952","DOI":"10.1158\/1078-0432.CCR-12-0920","article-title":"Multisite validation study to determine performance characteristics of a 92-gene molecular cancer classifier","volume":"18","author":"Kerr","year":"2012","journal-title":"Clin. Cancer Res."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/j.jmoldx.2012.10.001","article-title":"Blinded comparator study of immunohistochemical analysis versus a 92-gene cancer classifier in the diagnosis of the primary site in metastatic tumors","volume":"15","author":"Weiss","year":"2013","journal-title":"J. Mol. Diagn."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1200\/JCO.2012.43.3755","article-title":"Molecular gene expression profiling to predict the tissue of origin and direct site-specific therapy in patients with carcinoma of unknown primary site: A prospective trial of the sarah cannon research institute","volume":"31","author":"Hainsworth","year":"2013","journal-title":"J. Clin. Oncol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"320","DOI":"10.2353\/jmoldx.2006.050136","article-title":"A quantitative reverse transcriptase-polymerase chain reaction assay to identify metastatic carcinoma tissue of origin","volume":"8","author":"Talantov","year":"2006","journal-title":"J. Mol. Diagn."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1093\/jnci\/djt099","article-title":"Molecular profiling diagnosis in unknown primary cancer: Accuracy and ability to complement standard pathology","volume":"105","author":"Greco","year":"2013","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"4442","DOI":"10.1200\/JCO.2007.14.4378","article-title":"Molecular profiling of carcinoma of unknown primary and correlation with clinical evaluation","volume":"26","author":"Varadhachary","year":"2008","journal-title":"J. Clin. Oncol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.clcc.2011.08.001","article-title":"A retrospective study of treatment outcomes in patients with carcinoma of unknown primary site and a colorectal cancer molecular profile","volume":"11","author":"Hainsworth","year":"2012","journal-title":"Clin. Colorectal Cancer"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"e192597","DOI":"10.1001\/jamanetworkopen.2019.2597","article-title":"Application of a neural network whole transcriptome-based pan-cancer method for diagnosis of primary and metastatic cancers","volume":"2","author":"Grewal","year":"2019","journal-title":"JAMA Netw. Open"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1007\/s40291-015-0133-8","article-title":"Poorly differentiated neoplasms of unknown primary site: Diagnostic usefulness of a molecular cancer classifier assay","volume":"19","author":"Greco","year":"2015","journal-title":"Mol. Diagn. Ther."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1007\/s40801-016-0064-7","article-title":"Lung adenocarcinoma with anaplastic lymphoma kinase (alk) rearrangement presenting as carcinoma of unknown primary site: Recognition and treatment implications","volume":"3","author":"Hainsworth","year":"2016","journal-title":"Drugs Real World Outcomes"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"2657","DOI":"10.3892\/ol.2015.3572","article-title":"Gene expression profiling and its use in adenocarcinomas of unknown primary origin: A case report","volume":"10","author":"Cid","year":"2015","journal-title":"Oncol. Lett."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"4031","DOI":"10.1158\/0008-5472.CAN-04-3617","article-title":"An expression-based site of origin diagnostic method designed for clinical application to cancer of unknown origin","volume":"65","author":"Tothill","year":"2005","journal-title":"Cancer Res."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"1425","DOI":"10.1038\/sj.bjc.6604315","article-title":"Gene expression profiling may improve diagnosis in patients with carcinoma of unknown primary","volume":"98","author":"Bridgewater","year":"2008","journal-title":"Br. J. Cancer"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1002\/path.2915","article-title":"Microrna profiling for the identification of cancers with unknown primary tissue-of-origin","volume":"225","author":"Ferracin","year":"2011","journal-title":"J. Pathol."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1634\/theoncologist.2010-0305","article-title":"Accurate classification of metastatic brain tumors using a novel microrna-based test","volume":"16","author":"Mueller","year":"2011","journal-title":"Oncologist"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"4063","DOI":"10.1158\/1078-0432.CCR-10-2599","article-title":"Prospective gene signature study using microrna to identify the tissue of origin in patients with carcinoma of unknown primary","volume":"17","author":"Varadhachary","year":"2011","journal-title":"Clin. Cancer Res."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1101\/gr.119867.110","article-title":"A DNA methylation fingerprint of 1628 human samples","volume":"22","author":"Fernandez","year":"2012","journal-title":"Genome Res."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1186\/1476-4598-12-57","article-title":"Novel microrna-based assay demonstrates 92% agreement with diagnosis based on clinicopathologic and management data in a cohort of patients with carcinoma of unknown primary","volume":"12","author":"Pentheroudakis","year":"2013","journal-title":"Mol. Cancer"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"1386","DOI":"10.1016\/S1470-2045(16)30297-2","article-title":"Epigenetic profiling to classify cancer of unknown primary: A multicentre, retrospective analysis","volume":"17","author":"Moran","year":"2016","journal-title":"Lancet Oncol."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1200\/JCO.18.00771","article-title":"Randomized phase ii trial comparing site-specific treatment based on gene expression profiling with carboplatin and paclitaxel for patients with cancer of unknown primary site","volume":"37","author":"Hayashi","year":"2019","journal-title":"J. Clin. Oncol."},{"key":"ref_130","doi-asserted-by":"crossref","unstructured":"Kurahashi, I., Fujita, Y., Arao, T., Kurata, T., Koh, Y., Sakai, K., Matsumoto, K., Tanioka, M., Takeda, K., and Takiguchi, Y. (2013). A microarray-based gene expression analysis to identify diagnostic biomarkers for unknown primary cancer. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0063249"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"mdz394","DOI":"10.1093\/annonc\/mdz394","article-title":"A phase iii trial of empiric chemotherapy with cisplatin and gemcitabine or systemic treatment tailored by molecular gene expression analysis in patients with carcinomas of an unknown primary (cup) site (gefcapi 04)","volume":"30","author":"Fizazi","year":"2019","journal-title":"Ann. Oncol."},{"key":"ref_132","doi-asserted-by":"crossref","unstructured":"Opitz, L., Salinas-Riester, G., Grade, M., Jung, K., Jo, P., Emons, G., Ghadimi, B.M., Beissbarth, T., and Gaedcke, J. (2010). Impact of rna degradation on gene expression profiling. BMC Med. Genom., 3.","DOI":"10.1186\/1755-8794-3-36"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/S0002-9440(10)63093-3","article-title":"Measurement of gene expression in archival paraffin-embedded tissues: Development and performance of a 92-gene reverse transcriptase-polymerase chain reaction assay","volume":"164","author":"Cronin","year":"2004","journal-title":"Am. J. Pathol."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"4436","DOI":"10.1093\/nar\/27.22.4436","article-title":"Analysis of chemical modification of rna from formalin-fixed samples and optimization of molecular biology applications for such samples","volume":"27","author":"Masuda","year":"1999","journal-title":"Nucleic Acids Res."},{"key":"ref_135","doi-asserted-by":"crossref","unstructured":"Von Ahlfen, S., Missel, A., Bendrat, K., and Schlumpberger, M. (2007). Determinants of rna quality from ffpe samples. PLoS ONE, 2.","DOI":"10.1371\/journal.pone.0001261"},{"key":"ref_136","first-page":"519","article-title":"Microrna expression profiling outperforms mrna expression profiling in formalin-fixed paraffin-embedded tissues","volume":"2","author":"Liu","year":"2009","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1007\/s00428-013-1485-2","article-title":"High stability of micrornas in tissue samples of compromised quality","volume":"463","author":"Burgues","year":"2013","journal-title":"Virchows Arch."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"2257","DOI":"10.1073\/pnas.0510565103","article-title":"A microrna expression signature of human solid tumors defines cancer gene targets","volume":"103","author":"Volinia","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1038\/nature03702","article-title":"Microrna expression profiles classify human cancers","volume":"435","author":"Lu","year":"2005","journal-title":"Nature"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1586\/erm.10.11","article-title":"Micromarkers: Mirnas in cancer diagnosis and prognosis","volume":"10","author":"Ferracin","year":"2010","journal-title":"Expert Rev. Mol. Diagn."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1002\/path.2806","article-title":"Mirnas in human cancer","volume":"223","author":"Farazi","year":"2011","journal-title":"J. Pathol."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"447","DOI":"10.3389\/fonc.2018.00447","article-title":"Cancer site-specific multiple microrna quantification by droplet digital pcr","volume":"8","author":"Laprovitera","year":"2018","journal-title":"Front. Oncol."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.jmoldx.2013.10.001","article-title":"Efficient identification of mirnas for classification of tumor origin","volume":"16","author":"Sokilde","year":"2014","journal-title":"J. Mol. Diagn."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1038\/nbt1392","article-title":"Micrornas accurately identify cancer tissue origin","volume":"26","author":"Rosenfeld","year":"2008","journal-title":"Nat. Biotechnol."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"814","DOI":"10.1038\/modpathol.2010.57","article-title":"Validation of a microrna-based qrt-pcr test for accurate identification of tumor tissue origin","volume":"23","author":"Rosenwald","year":"2010","journal-title":"Mod. Pathol."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1634\/theoncologist.2011-0466","article-title":"A second-generation microrna-based assay for diagnosing tumor tissue origin","volume":"17","author":"Meiri","year":"2012","journal-title":"Oncologist"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"263","DOI":"10.3892\/mco.2016.912","article-title":"Cancer of unknown primary ultimately diagnosed as male breast cancer: A rare case report","volume":"5","author":"Rigakos","year":"2016","journal-title":"Mol. Clin. Oncol."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1093\/bioinformatics\/btx622","article-title":"Tumor origin detection with tissue-specific mirna and DNA methylation markers","volume":"34","author":"Tang","year":"2018","journal-title":"Bioinformatics"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1038\/ng.2764","article-title":"The cancer genome atlas pan-cancer analysis project","volume":"45","author":"Weinstein","year":"2013","journal-title":"Nat. Genet."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/j.cell.2018.03.022","article-title":"Cell-of-origin patterns dominate the molecular classification of 10,000 tumors from 33 types of cancer","volume":"173","author":"Hoadley","year":"2018","journal-title":"Cell"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1016\/j.cell.2014.06.049","article-title":"Multiplatform analysis of 12 cancer types reveals molecular classification within and across tissues of origin","volume":"158","author":"Hoadley","year":"2014","journal-title":"Cell"},{"key":"ref_152","doi-asserted-by":"crossref","unstructured":"Tsimberidou, A.M., Hong, D.S., Ye, Y., Cartwright, C., Wheler, J.J., Falchook, G.S., Naing, A., Fu, S., Piha-Paul, S., and Janku, F. (2017). Initiative for molecular profiling and advanced cancer therapy (impact): An md anderson precision medicine study. JCO Precis. Oncol., 2017.","DOI":"10.1200\/PO.17.00002"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1001\/jamaoncol.2014.216","article-title":"Comprehensive genomic profiling of carcinoma of unknown primary site: New routes to targeted therapies","volume":"1","author":"Ross","year":"2015","journal-title":"JAMA Oncol."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1186\/s12967-018-1564-x","article-title":"Genetic characterisation of molecular targets in carcinoma of unknown primary","volume":"16","author":"Clynick","year":"2018","journal-title":"J. Transl. Med."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"3015","DOI":"10.1093\/annonc\/mdx545","article-title":"Clinical and molecular characterization of patients with cancer of unknown primary in the modern era","volume":"28","author":"Varghese","year":"2017","journal-title":"Ann. Oncol."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1002\/path.4251","article-title":"Massively-parallel sequencing assists the diagnosis and guided treatment of cancers of unknown primary","volume":"231","author":"Tothill","year":"2013","journal-title":"J. Pathol."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"12440","DOI":"10.18632\/oncotarget.2574","article-title":"Comprehensive tumor profiling identifies numerous biomarkers of drug response in cancers of unknown primary site: Analysis of 1806 cases","volume":"5","author":"Gatalica","year":"2014","journal-title":"Oncotarget"},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"47","DOI":"10.18632\/oncoscience.352","article-title":"Next generation sequencing of carcinoma of unknown primary reveals novel combinatorial strategies in a heterogeneous mutational landscape","volume":"4","author":"Subbiah","year":"2017","journal-title":"Oncoscience"},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1007\/s10585-014-9666-1","article-title":"Mutational profiling of the ras, pi3k, met and b-catenin pathways in cancer of unknown primary: A retrospective study of the hellenic cooperative oncology group","volume":"31","author":"Pentheroudakis","year":"2014","journal-title":"Clin. Exp. Metastasis"},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"44322","DOI":"10.18632\/oncotarget.10035","article-title":"Molecular driver alterations and their clinical relevance in cancer of unknown primary site","volume":"7","author":"Loffler","year":"2016","journal-title":"Oncotarget"},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.ejca.2018.02.021","article-title":"Comprehensive analysis of cancers of unknown primary for the biomarkers of response to immune checkpoint blockade therapy","volume":"94","author":"Gatalica","year":"2018","journal-title":"Eur. J. Cancer"},{"key":"ref_162","doi-asserted-by":"crossref","unstructured":"Vikesa, J., Moller, A.K., Kaczkowski, B., Borup, R., Winther, O., Henao, R., Krogh, A., Perell, K., Jensen, F., and Daugaard, G. (2015). Cancers of unknown primary origin (cup) are characterized by chromosomal instability (cin) compared to metastasis of know origin. BMC Cancer, 15.","DOI":"10.1186\/s12885-015-1128-x"},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1002\/humu.21374","article-title":"Met mutations in cancers of unknown primary origin (cups)","volume":"32","author":"Stella","year":"2011","journal-title":"Hum. Mutat."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1038\/nm.4333","article-title":"Mutational landscape of metastatic cancer revealed from prospective clinical sequencing of 10,000 patients","volume":"23","author":"Zehir","year":"2017","journal-title":"Nat. Med."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1158\/2159-8290.CD-12-0095","article-title":"The cbio cancer genomics portal: An open platform for exploring multidimensional cancer genomics data","volume":"2","author":"Cerami","year":"2012","journal-title":"Cancer Discov."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1002\/path.4672","article-title":"Massively parallel sequencing of phyllodes tumours of the breast reveals actionable mutations, and tert promoter hotspot mutations and tert gene amplification as likely drivers of progression","volume":"238","author":"Piscuoglio","year":"2016","journal-title":"J. Pathol."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1126\/science.1229259","article-title":"Highly recurrent tert promoter mutations in human melanoma","volume":"339","author":"Huang","year":"2013","journal-title":"Science"},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"818","DOI":"10.1158\/2159-8290.CD-17-0151","article-title":"Aacr project genie: Powering precision medicine through an international consortium","volume":"7","author":"Consortium","year":"2017","journal-title":"Cancer Discov."},{"key":"ref_169","doi-asserted-by":"crossref","unstructured":"Chakravarty, D., Gao, J., Phillips, S.M., Kundra, R., Zhang, H., Wang, J., Rudolph, J.E., Yaeger, R., Soumerai, T., and Nissan, M.H. (2017). Oncokb: A precision oncology knowledge base. JCO Precis. Oncol., 2017.","DOI":"10.1200\/PO.17.00011"},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1038\/nature10868","article-title":"Unresponsiveness of colon cancer to braf(v600e) inhibition through feedback activation of egfr","volume":"483","author":"Prahallad","year":"2012","journal-title":"Nature"},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"1324","DOI":"10.1016\/S1470-2045(15)00188-6","article-title":"Molecularly targeted therapy based on tumour molecular profiling versus conventional therapy for advanced cancer (shiva): A multicentre, open-label, proof-of-concept, randomised, controlled phase 2 trial","volume":"16","author":"Delord","year":"2015","journal-title":"Lancet Oncol."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1158\/2159-8290.CD-16-1396","article-title":"High-throughput genomics and clinical outcome in hard-to-treat advanced cancers: Results of the moscato 01 trial","volume":"7","author":"Massard","year":"2017","journal-title":"Cancer Discov."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1093\/annonc\/mdz080","article-title":"Molecular screening program to select molecular-based recommended therapies for metastatic cancer patients: Analysis from the profiler trial","volume":"30","author":"Tredan","year":"2019","journal-title":"Ann. Oncol."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"a001180","DOI":"10.1101\/mcs.a001180","article-title":"Integration of genomics and histology revises diagnosis and enables effective therapy of refractory cancer of unknown primary with pdl1 amplification","volume":"2","author":"Groschel","year":"2016","journal-title":"Cold Spring Harb. Mol. Case Stud."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1159\/000365326","article-title":"Durable response to crizotinib in a met-amplified, kras-mutated carcinoma of unknown primary","volume":"7","author":"Palma","year":"2014","journal-title":"Case Rep. Oncol."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"e237","DOI":"10.1200\/JCO.2012.44.3937","article-title":"Molecular profiling for druggable genetic abnormalities in carcinoma of unknown primary","volume":"31","author":"Tan","year":"2013","journal-title":"J. Clin. Oncol."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1159\/000367780","article-title":"A poorly differentiated malignant neoplasm lacking lung markers harbors an eml4-alk rearrangement and responds to crizotinib","volume":"7","author":"Chung","year":"2014","journal-title":"Case Rep. Oncol."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1097\/PPO.0b013e3181c6aa89","article-title":"Paclitaxel\/carboplatin\/etoposide versus gemcitabine\/irinotecan in the first-line treatment of patients with carcinoma of unknown primary site: A randomized, phase iii sarah cannon oncology research consortium trial","volume":"16","author":"Hainsworth","year":"2010","journal-title":"Cancer J."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"3072","DOI":"10.1200\/JCO.2019.37.15_suppl.3072","article-title":"3072 clinical impact of tissue of origin testing and mutation profiling in the solving unknown primary cancer (super) national prospective study: Experience of the first two years","volume":"37","author":"Mileshkin","year":"2019","journal-title":"J. Clin. Oncol."},{"key":"ref_180","doi-asserted-by":"crossref","unstructured":"Marquard, A.M., Birkbak, N.J., Thomas, C.E., Favero, F., Krzystanek, M., Lefebvre, C., Ferte, C., Jamal-Hanjani, M., Wilson, G.A., and Shafi, S. (2015). Tumortracer: A method to identify the tissue of origin from the somatic mutations of a tumor specimen. BMC Med. Genom., 8.","DOI":"10.1186\/s12920-015-0130-0"},{"key":"ref_181","unstructured":"TumorTracer (2020, September 20). Tumortracer. Available online: http:\/\/www.cbs.dtu.dk\/services\/TumorTracer."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1038\/s41467-019-13825-8","article-title":"A deep learning system accurately classifies primary and metastatic cancers using passenger mutation patterns","volume":"11","author":"Jiao","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1200\/PO.18.00002","article-title":"Mutational signature and transcriptomic classification analyses as the decisive diagnostic tools for a cancer of unknown primary","volume":"2","author":"Bagge","year":"2018","journal-title":"JCO Precis. Oncol."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1001\/jamaoncol.2019.3985","article-title":"Development of genome-derived tumor type prediction to inform clinical cancer care","volume":"6","author":"Penson","year":"2019","journal-title":"JAMA Oncol."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1186\/s13073-017-0424-2","article-title":"Analysis of 100,000 human cancer genomes reveals the landscape of tumor mutational burden","volume":"9","author":"Chalmers","year":"2017","journal-title":"Genome Med."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"2509","DOI":"10.1056\/NEJMoa1500596","article-title":"Pd-1 blockade in tumors with mismatch-repair deficiency","volume":"372","author":"Le","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1126\/science.aan6733","article-title":"Mismatch repair deficiency predicts response of solid tumors to pd-1 blockade","volume":"357","author":"Le","year":"2017","journal-title":"Science"},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"2018","DOI":"10.1056\/NEJMoa1501824","article-title":"Pembrolizumab for the treatment of non-small-cell lung cancer","volume":"372","author":"Garon","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"1789","DOI":"10.1056\/NEJMoa1802357","article-title":"Adjuvant pembrolizumab versus placebo in resected stage iii melanoma","volume":"378","author":"Eggermont","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"4238","DOI":"10.1158\/0008-5472.CAN-17-0628","article-title":"Utility of genomic analysis in circulating tumor DNA from patients with carcinoma of unknown primary","volume":"77","author":"Kato","year":"2017","journal-title":"Cancer Res."},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"v934","DOI":"10.1093\/annonc\/mdz394.094","article-title":"1983pd pr comprehensive genomic profiling (cgp) of carcinoma of unknown primary origin (cup): Retrospective molecular classification of potentially eligible patients (pts) for targeted or immunotherapy treatment (tx) using the prospective cupisco trial\u2019s criteria","volume":"30","author":"Ross","year":"2019","journal-title":"Ann. Oncol."},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1056\/NEJMoa1113205","article-title":"Intratumor heterogeneity and branched evolution revealed by multiregion sequencing","volume":"366","author":"Gerlinger","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"ref_193","doi-asserted-by":"crossref","unstructured":"Wong, S.Q., Li, J., Tan, A.Y., Vedururu, R., Pang, J.M., Do, H., Ellul, J., Doig, K., Bell, A., and MacArthur, G.A. (2014). Sequence artefacts in a prospective series of formalin-fixed tumours tested for mutations in hotspot regions by massively parallel sequencing. BMC Med. Genom., 7.","DOI":"10.1186\/1755-8794-7-23"},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.ejca.2018.09.035","article-title":"Liquid biopsy: A new diagnostic, predictive and prognostic window in cancers of unknown primary","volume":"105","author":"Khaled","year":"2018","journal-title":"Eur. J. Cancer"},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"12021","DOI":"10.1200\/JCO.2018.36.15_suppl.12021","article-title":"Development of a comprehensive cell-free DNA (cfdna) assay for early detection of multiple tumor types: The circulating cell-free genome atlas (ccga) study","volume":"36","author":"Klein","year":"2018","journal-title":"J. Clin. Oncol."},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1080\/15384047.2016.1141839","article-title":"Identifying cancer origin using circulating tumor cells","volume":"17","author":"Lu","year":"2016","journal-title":"Cancer Biol. Ther."},{"key":"ref_197","first-page":"E1826","article-title":"Identification of tissue-specific cell death using methylation patterns of circulating DNA","volume":"113","author":"Neiman","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1016\/j.ccell.2015.09.018","article-title":"Rna-seq of tumor-educated platelets enables blood-based pan-cancer, multiclass, and molecular pathway cancer diagnostics","volume":"28","author":"Best","year":"2015","journal-title":"Cancer Cell"},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"1351","DOI":"10.1093\/annonc\/mdy134","article-title":"Methylation in cell-free DNA for early cancer detection","volume":"29","author":"Corcoran","year":"2018","journal-title":"Ann. Oncol."},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"9707","DOI":"10.18632\/oncotarget.7110","article-title":"Detection rate of actionable mutations in diverse cancers using a biopsy-free (blood) circulating tumor cell DNA assay","volume":"7","author":"Schwaederle","year":"2016","journal-title":"Oncotarget"},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"1044","DOI":"10.1016\/j.cell.2020.07.009","article-title":"Extracellular vesicle and particle biomarkers define multiple human cancers","volume":"182","author":"Hoshino","year":"2020","journal-title":"Cell"},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"3662","DOI":"10.18632\/oncotarget.6657","article-title":"A multiplexed marker-based algorithm for diagnosis of carcinoma of unknown primary using circulating tumor cells","volume":"7","author":"Matthew","year":"2016","journal-title":"Oncotarget"},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1186\/s13059-017-1191-5","article-title":"Cancerlocator: Non-invasive cancer diagnosis and tissue-of-origin prediction using methylation profiles of cell-free DNA","volume":"18","author":"Kang","year":"2017","journal-title":"Genome Biol."},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1158\/2159-8290.CD-13-1014","article-title":"Blood-based analyses of cancer: Circulating tumor cells and circulating tumor DNA","volume":"4","author":"Haber","year":"2014","journal-title":"Cancer Discov."},{"key":"ref_205","first-page":"3165","article-title":"Utility of measuring circulating tumor cell counts to assess the efficacy of treatment for carcinomas of unknown primary origin","volume":"34","author":"Komine","year":"2014","journal-title":"Anticancer Res."},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"x278","DOI":"10.1093\/annonc\/mds318","article-title":"Cup: Looking for a missing primary site and its biology","volume":"23","author":"Pentheroudakis","year":"2012","journal-title":"Ann. Oncol."},{"key":"ref_207","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1016\/j.molonc.2014.12.003","article-title":"Circulating tumor DNA as a non-invasive substitute to metastasis biopsy for tumor genotyping and personalized medicine in a prospective trial across all tumor types","volume":"9","author":"Lebofsky","year":"2015","journal-title":"Mol. Oncol."},{"key":"ref_208","doi-asserted-by":"crossref","first-page":"2960","DOI":"10.1158\/1078-0432.CCR-15-2470","article-title":"Circulating cell-free tumor DNA analysis of 50 genes by next-generation sequencing in the prospective moscato trial","volume":"22","author":"Jovelet","year":"2016","journal-title":"Clin. Cancer Res."},{"key":"ref_209","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1186\/s13045-018-0610-8","article-title":"Met alterations detected in blood-derived circulating tumor DNA correlate with bone metastases and poor prognosis","volume":"11","author":"Ikeda","year":"2018","journal-title":"J. Hematol. Oncol."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/13\/3\/451\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:15:09Z","timestamp":1760159709000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/13\/3\/451"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,25]]},"references-count":209,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2021,2]]}},"alternative-id":["cancers13030451"],"URL":"https:\/\/doi.org\/10.3390\/cancers13030451","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,25]]}}}