{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T04:15:47Z","timestamp":1772165747014,"version":"3.50.1"},"reference-count":27,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,3,14]],"date-time":"2020-03-14T00:00:00Z","timestamp":1584144000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2020,3,14]],"date-time":"2020-03-14T00:00:00Z","timestamp":1584144000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007369","name":"Fukuoka Foundation for Sound Health","doi-asserted-by":"publisher","award":["2014"],"award-info":[{"award-number":["2014"]}],"id":[{"id":"10.13039\/501100007369","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Cancer"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Periampullary cancers (PAC) including pancreatic, ampulla of Vater (AOV), and common bile duct (CBD) cancers are highly aggressive with a lack of useful prognostic markers beyond T stage. However, T staging can be biased due to the anatomic complexity of this region. Recently, several markers related to cancer stem cells and epithelial-mesenchymal transition (EMT) such as octamer transcription factor-4 (Oct4) and fibroblast growth factor receptor 1 (FGFR1) respectively, have been proposed as new promising markers in other solid cancers. The aim of this study was to assess the expression and prognostic significance of stem cell\/EMT markers in PACs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Formalin-fixed, paraffin-embedded tissues of surgically excised PACs from the laboratory archives from 1998 to 2014 were evaluated by immunohistochemical staining for stem cell\/EMT markers using tissue microarray. The clinicopathologic parameters were documented and statistically analyzed with the immunohistochemical findings. Survival and recurrence data were collected and analyzed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 126 PAC cases were evaluated. The average age was 63\u2009years, with 76 male and 50 female patient samples. Age less than 74\u2009years, AOV cancers, lower T &amp; N stage, lower tumor size, no lymphatic, vascular, perineural invasion and histologic well differentiation, intestinal type, no fibrosis, severe inflammation were significantly associated with the better overall survival High expression levels of FGFR1 as well as CK20, CDX2, and VEGF were significantly related to better overall survival, while other stem cell markers were not related. Similar findings were observed for tumor recurrence using disease-free survival.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In addition to other clinicopathologic parameters, severe fibrosis was related to frequent tumor recurrence, and high FGFR1 expression was associated with better overall survival. Histologic changes such as extensive fibrosis need to be investigated further in relation to EMT of PACs.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12885-020-6673-2","type":"journal-article","created":{"date-parts":[[2020,3,14]],"date-time":"2020-03-14T07:03:20Z","timestamp":1584169400000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Prognostic significance of stem cell\/ epithelial-mesenchymal transition markers in periampullary\/pancreatic cancers: FGFR1 is a promising prognostic marker"],"prefix":"10.1186","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8615-3064","authenticated-orcid":false,"given":"Yosep","family":"Chong","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nishant","family":"Thakur","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kwang Yeol","family":"Paik","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eun Jung","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chang Suk","family":"Kang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,3,14]]},"reference":[{"key":"6673_CR1","volume-title":"Rosai and Ackerman\u2019s surgical pathology, 10th edn. Edinburgh","author":"J Rosai","year":"2011","unstructured":"Rosai J, Ackerman LV, Rosai J. Rosai and Ackerman\u2019s surgical pathology, 10th edn. Edinburgh. New York: Mosby; 2011."},{"issue":"3","key":"6673_CR2","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1053\/j.semdp.2012.08.010","volume":"29","author":"NV Adsay","year":"2012","unstructured":"Adsay NV, Bagci P, Tajiri T, Oliva I, Ohike N, Balci S, Gonzalez RS, Basturk O, Jang KT, Roa JC. Pathologic staging of pancreatic, ampullary, biliary, and gallbladder cancers: pitfalls and practical limitations of the current AJCC\/UICC TNM staging system and opportunities for improvement. Semin Diagn Pathol. 2012;29(3):127\u201341.","journal-title":"Semin Diagn Pathol"},{"key":"6673_CR3","volume-title":"American joint committee on Cancer.: AJCC cancer staging manual, 7th edn","author":"SB Edge","year":"2010","unstructured":"Edge SB. American joint committee on Cancer.: AJCC cancer staging manual, 7th edn. New York: Springer; 2010."},{"key":"6673_CR4","doi-asserted-by":"publisher","DOI":"10.1038\/oncsis.2013.23","volume":"2","author":"M Herreros-Villanueva","year":"2013","unstructured":"Herreros-Villanueva M, Zhang JS, Koenig A, Abel EV, Smyrk TC, Bamlet WR, de Narvajas AA, Gomez TS, Simeone DM, Bujanda L, et al. SOX2 promotes dedifferentiation and imparts stem cell-like features to pancreatic cancer cells. Oncogenesis. 2013;2:e61.","journal-title":"Oncogenesis"},{"issue":"3","key":"6673_CR5","doi-asserted-by":"publisher","first-page":"1335","DOI":"10.3892\/mmr.2014.2367","volume":"10","author":"H Lin","year":"2014","unstructured":"Lin H, Sun LH, Han W, He TY, Xu XJ, Cheng K, Geng C, Su LD, Wen H, Wang XY, et al. Knockdown of OCT4 suppresses the growth and invasion of pancreatic cancer cells through inhibition of the AKT pathway. Mol Med Rep. 2014;10(3):1335\u201342.","journal-title":"Mol Med Rep"},{"issue":"1","key":"6673_CR6","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1016\/j.canlet.2013.07.009","volume":"340","author":"Y Lu","year":"2013","unstructured":"Lu Y, Zhu H, Shan H, Lu J, Chang X, Li X, Lu J, Fan X, Zhu S, Wang Y, et al. Knockdown of Oct4 and Nanog expression inhibits the stemness of pancreatic cancer cells. Cancer Lett. 2013;340(1):113\u201323.","journal-title":"Cancer Lett"},{"issue":"9","key":"6673_CR7","doi-asserted-by":"publisher","first-page":"2247","DOI":"10.3748\/wjg.v20.i9.2247","volume":"20","author":"M Herreros-Villanueva","year":"2014","unstructured":"Herreros-Villanueva M, Bujanda L, Billadeau DD, Zhang JS. Embryonic stem cell factors and pancreatic cancer. World J Gastroenterol. 2014;20(9):2247\u201354.","journal-title":"World J Gastroenterol"},{"key":"6673_CR8","doi-asserted-by":"crossref","unstructured":"Roche J. The Epithelial-to-Mesenchymal Transition in Cancer. Cancers (Basel). 2018:10(2).","DOI":"10.3390\/cancers10020052"},{"key":"6673_CR9","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1146\/annurev.biochem.69.1.373","volume":"69","author":"SR Hubbard","year":"2000","unstructured":"Hubbard SR, Till JH. Protein tyrosine kinase structure and function. Annu Rev Biochem. 2000;69:373\u201398.","journal-title":"Annu Rev Biochem"},{"issue":"5","key":"6673_CR10","doi-asserted-by":"publisher","first-page":"633","DOI":"10.1002\/mc.22309","volume":"55","author":"DE Jung","year":"2016","unstructured":"Jung DE, Kim JM, Kim C, Song SY. Embigin is overexpressed in pancreatic ductal adenocarcinoma and regulates cell motility through epithelial to mesenchymal transition via the TGF- pathway. Mol Carcinogen. 2016;55(5):633\u201345.","journal-title":"Mol Carcinogen"},{"issue":"5","key":"6673_CR11","doi-asserted-by":"publisher","first-page":"1930","DOI":"10.1159\/000489382","volume":"46","author":"YP Peng","year":"2018","unstructured":"Peng YP, Zhu Y, Yin LD, Wei JS, Liu XC, Zhu XL, Miao Y. PIK3R3 promotes metastasis of pancreatic Cancer via ZEB1 induced epithelial-Mesenchymal transition. Cell Physiol Biochem. 2018;46(5):1930\u20138.","journal-title":"Cell Physiol Biochem"},{"key":"6673_CR12","doi-asserted-by":"publisher","DOI":"10.7717\/peerj.4893","volume":"6","author":"S Zhang","year":"2018","unstructured":"Zhang S, Huang X, Tian Y, Aimaiti S, Zhang J, Zhao J, Chen Y, Wang C. Clinicopathologic characteristics, laboratory parameters, treatment protocols, and outcomes of pancreatic cancer: a retrospective cohort study of 1433 patients in China. PeerJ. 2018;6:e4893.","journal-title":"PeerJ"},{"key":"6673_CR13","doi-asserted-by":"publisher","first-page":"247","DOI":"10.12659\/MSM.899005","volume":"23","author":"D Pu","year":"2017","unstructured":"Pu D, Liu J, Li Z, Zhu J, Hou M. Fibroblast growth factor receptor 1 (FGFR1), partly related to vascular endothelial growth factor receptor 2 (VEGFR2) and microvessel density, is an independent prognostic factor for non-small cell lung Cancer. Med Sci Monit. 2017;23:247\u201357.","journal-title":"Med Sci Monit"},{"issue":"1","key":"6673_CR14","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1186\/1756-9966-31-103","volume":"31","author":"E Brunello","year":"2012","unstructured":"Brunello E, Brunelli M, Bogina G, Cali\u00f2 A, Manfrin E, Nottegar A, Vergine M, Molino A, Bria E, Massari F, et al. FGFR-1 amplification in metastatic lymph-nodal and haematogenous lobular breast carcinoma. J Exp Clin Cancer Res. 2012;31(1):103.","journal-title":"J Exp Clin Cancer Res"},{"issue":"62","key":"6673_CR15","doi-asserted-by":"publisher","first-page":"62ra93","DOI":"10.1126\/scitranslmed.3001451","volume":"2","author":"J Weiss","year":"2010","unstructured":"Weiss J, Sos ML, Seidel D, Peifer M, Zander T, Heuckmann JM, Ullrich RT, Menon R, Maier S, Soltermann A, et al. Frequent and Focal FGFR1 Amplification Associates with Therapeutically Tractable FGFR1 Dependency in Squamous Cell Lung Cancer. Sci Transl Med. 2010;2(62):62ra93.","journal-title":"Sci Transl Med"},{"issue":"2","key":"6673_CR16","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1016\/j.ccell.2017.07.007","volume":"32","author":"Cancer Genome Atlas Research Network","year":"2017","unstructured":"Cancer Genome Atlas Research Network. Electronic address aadhe, Cancer genome atlas research N: integrated genomic characterization of pancreatic ductal adenocarcinoma. Cancer Cell. 2017;32(2):185\u2013203 e113.","journal-title":"Cancer Cell"},{"issue":"1","key":"6673_CR17","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1080\/15384047.2017.1394541","volume":"19","author":"B Chen","year":"2018","unstructured":"Chen B, Liu S, Gan L, Wang J, Hu B, Xu H, Tong R, Yang H, Cristina I, Xue J, et al. FGFR1 signaling potentiates tumor growth and predicts poor prognosis in esophageal squamous cell carcinoma patients. Cancer Biol Ther. 2018;19(1):76\u201386.","journal-title":"Cancer Biol Ther"},{"issue":"5","key":"6673_CR18","doi-asserted-by":"publisher","first-page":"547","DOI":"10.1007\/s00428-014-1634-2","volume":"465","author":"AN Seo","year":"2014","unstructured":"Seo AN, Jin Y, Lee HJ, Sun PL, Kim H, Jheon S, Kim K, Lee CT, Chung JH. FGFR1 amplification is associated with poor prognosis and smoking in non-small-cell lung cancer. Virchows Arch. 2014;465(5):547\u201358.","journal-title":"Virchows Arch"},{"issue":"1","key":"6673_CR19","doi-asserted-by":"publisher","first-page":"374","DOI":"10.1186\/s12967-018-1743-9","volume":"16","author":"F Haq","year":"2018","unstructured":"Haq F, Sung YN, Park I, Kayani MA, Yousuf F, Hong SM, Ahn SM. FGFR1 expression defines clinically distinct subtypes in pancreatic cancer. J Transl Med. 2018;16(1):374.","journal-title":"J Transl Med"},{"issue":"1","key":"6673_CR20","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1186\/s12943-018-0927-5","volume":"18","author":"D Thomas","year":"2019","unstructured":"Thomas D, Radhakrishnan P. Tumor-stromal crosstalk in pancreatic cancer and tissue fibrosis. Mol Cancer. 2019;18(1):14.","journal-title":"Mol Cancer"},{"issue":"51","key":"6673_CR21","doi-asserted-by":"publisher","first-page":"29574","DOI":"10.18632\/oncotarget.25636","volume":"9","author":"D Ikuta","year":"2018","unstructured":"Ikuta D, Miyake T, Shimizu T, Sonoda H, Mukaisho K-I, Tokuda A, Ueki T, Sugihara H, Tani M. Fibrosis in metastatic lymph nodes is clinically correlated to poor prognosis in colorectal cancer. Oncotarget. 2018;9(51):29574\u201386.","journal-title":"Oncotarget"},{"key":"6673_CR22","doi-asserted-by":"publisher","first-page":"9207616","DOI":"10.1155\/2017\/9207616","volume":"2017","author":"D Myoteri","year":"2017","unstructured":"Myoteri D, Dellaportas D, Lykoudis PM, Apostolopoulos A, Marinis A, Zizi-Sermpetzoglou A. Prognostic evaluation of Vimentin expression in correlation with Ki67 and CD44 in surgically resected pancreatic ductal adenocarcinoma. Gastroenterol Res Pract. 2017;2017:9207616.","journal-title":"Gastroenterol Res Pract"},{"issue":"10","key":"6673_CR23","doi-asserted-by":"publisher","first-page":"2239","DOI":"10.1002\/(SICI)1097-0142(20000515)88:10<2239::AID-CNCR6>3.0.CO;2-V","volume":"88","author":"Y Seo","year":"2000","unstructured":"Seo Y, Baba H, Fukuda T, Takashima M, Sugimachi K. High expression of vascular endothelial growth factor is associated with liver metastasis and a poor prognosis for patients with ductal pancreatic adenocarcinoma. Cancer. 2000;88(10):2239\u201345.","journal-title":"Cancer"},{"issue":"4","key":"6673_CR24","first-page":"1233","volume":"29","author":"Q Wang","year":"2009","unstructured":"Wang Q, He W, Lu C, Wang Z, Wang J, Giercksky KE, Nesland JM, Suo Z. Oct3\/4 and Sox2 are significantly associated with an unfavorable clinical outcome in human esophageal squamous cell carcinoma. Anticancer Res. 2009;29(4):1233\u201341.","journal-title":"Anticancer Res"},{"issue":"6","key":"6673_CR25","doi-asserted-by":"publisher","first-page":"2093","DOI":"10.3892\/ijo.2012.1648","volume":"41","author":"K Quint","year":"2012","unstructured":"Quint K, Tonigold M, Di Fazio P, Montalbano R, Lingelbach S, Ruckert F, Alinger B, Ocker M, Neureiter D. Pancreatic cancer cells surviving gemcitabine treatment express markers of stem cell differentiation and epithelial-mesenchymal transition. Int J Oncol. 2012;41(6):2093\u2013102.","journal-title":"Int J Oncol"},{"issue":"1\u20132","key":"6673_CR26","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1159\/000178882","volume":"9","author":"K Quint","year":"2009","unstructured":"Quint K, Stintzing S, Alinger B, Hauser-Kronberger C, Dietze O, Gahr S, Hahn EG, Ocker M, Neureiter D. The expression pattern of PDX-1, SHH, patched and Gli-1 is associated with pathological and clinical features in human pancreatic cancer. Pancreatology. 2009;9(1\u20132):116\u201326.","journal-title":"Pancreatology"},{"key":"6673_CR27","unstructured":"Amin MB, American Joint Committee on Cancer., American Cancer Society.: AJCC cancer staging manual, Eight edition \/ editor-in-chief, Mahul B. Amin, MD, FCAP ; editors, Stephen B. Edge, MD, FACS and 16 others ; Donna M. Gress, RHIT, CTR - Technical editor ; Laura R. Meyer, CAPM - Managing editor. edn. Chicago: American Joint Committee on Cancer, Springer; 2017."}],"container-title":["BMC Cancer"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12885-020-6673-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s12885-020-6673-2\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12885-020-6673-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,3,13]],"date-time":"2021-03-13T19:11:59Z","timestamp":1615662719000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmccancer.biomedcentral.com\/articles\/10.1186\/s12885-020-6673-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,3,14]]},"references-count":27,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020,12]]}},"alternative-id":["6673"],"URL":"https:\/\/doi.org\/10.1186\/s12885-020-6673-2","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.2.15418\/v1","asserted-by":"object"},{"id-type":"doi","id":"10.21203\/rs.2.15418\/v2","asserted-by":"object"},{"id-type":"doi","id":"10.21203\/rs.2.15418\/v3","asserted-by":"object"}]},"ISSN":["1471-2407"],"issn-type":[{"value":"1471-2407","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,3,14]]},"assertion":[{"value":"19 September 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 February 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 March 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"This study was reviewed and approved by the Institutional Review Board of the Catholic University of Korea (SC14SISI0052) with a waiver of informed consent because the samples used in this study are legitimate according to the Bioethic Law and the data and images in this study were entirely deidentified.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"216"}}