{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T11:45:55Z","timestamp":1789472755179,"version":"build-2803163510"},"reference-count":51,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2020,7,6]],"date-time":"2020-07-06T00:00:00Z","timestamp":1593993600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"research fund from Chosun University Hospital","award":["2019"],"award-info":[{"award-number":["2019"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Background: The present study aims to evaluate the diagnostic roles of various immunohistochemical (IHC) markers in thymic tumors, including thymic carcinoma (TC) and thymoma (TM). Methods: Eligible studies were obtained by searching the PubMed databases and screening the searched articles. Thirty-eight articles were used in the present meta-analysis and included 636 TCs and 1861 TMs. Besides, for IHC markers with statistical significance, a diagnostic test accuracy review was performed. Results: The comparison of various IHC expressions between TC and TM was performed for 32 IHC markers. Among these IHC markers, there were significant differences between TC and TM for beta-5t, B-cell lymphoma 2 (Bcl-2), calretinin, CD1a, CD5, carcinoembryonic antigen (CEA), cytokeratin19 (CK19), CD117, glucose transporter 1 (Glut-1), insulin-like growth factor 1 receptor (IGF-1R), mesothelin, MOC31, mucin1 (MUC1), p21, and terminal deoxynucleotidyl transferase (TdT). Markers with higher expressions in TCs were Bcl-2, calretinin, CD5, CEA, CD117, Glut-1, IGF-1R, mesothelin, MOC31, MUC1, and p21. Among these markers, there were no significant differences between TC and TM type B3 in immunohistochemistries for Bcl-2 and CK19. On the other hand, \u03b2-catenin and CD205 showed a considerable difference in IHC expressions between TC and TM type B3, but not between TC and overall TM. In diagnostic test accuracy review, MUC1 and beta-5t were the most useful markers for TC and TM, respectively. Conclusions: Taken together, our results showed that the expression rates for various IHC markers significantly differed between TC and TM. The IHC panel can be useful for differentiation from limited biopsied specimens in daily practice.<\/jats:p>","DOI":"10.3390\/diagnostics10070460","type":"journal-article","created":{"date-parts":[[2020,7,6]],"date-time":"2020-07-06T11:07:42Z","timestamp":1594033662000},"page":"460","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Diagnostic Roles of Immunohistochemistry in Thymic Tumors: Differentiation between Thymic Carcinoma and Thymoma"],"prefix":"10.3390","volume":"10","author":[{"given":"Jae-Han","family":"Jeong","sequence":"first","affiliation":[{"name":"Department of Thoracic and Cardiovascular Surgery, Chosun University Hospital, Chosun University School of Medicine, Gwangju 61453, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jung-Soo","family":"Pyo","sequence":"additional","affiliation":[{"name":"Department of Pathology, Daejeon Eulji University Hospial, Eulji University School of Medicine, Daejeon 35233, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nae-Yu","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Daejeon Eulji University Hospital, Eulji University School of Medicine, Daejeon 35233, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4300-3469","authenticated-orcid":false,"given":"Dong-Wook","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Pathology, Chungnam National University Sejong Hospital, 20 Bodeum 7-ro, Sejong 30099, Korea"},{"name":"Department of Pathology, Chungnam National University School of Medicine, 266 Munhwa Street, Daejeon 35015, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,7,6]]},"reference":[{"key":"ref_1","unstructured":"Travis, W.D., Brambilla, E., Burke, A.P., Marx, A., and Nicholson, A.G. (2015). WHO Classification of Tumours of the Lung, Pleura, Thymus and Heart, International Agency for Research on Cancer. [4th ed.]."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"4602","DOI":"10.21037\/jtd.2019.10.56","article-title":"Expression and significance of c-kit and epithelial-mesenchymal transition (EMT) molecules in thymic epithelial tumors (TETs)","volume":"11","author":"Wu","year":"2019","journal-title":"J. Thorac. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"4820","DOI":"10.1200\/JCO.2011.36.0487","article-title":"Thymic malignancies: From clinical management to targeted therapies","volume":"29","author":"Kelly","year":"2011","journal-title":"J. Clin. Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1097\/JTO.0000000000000154","article-title":"ITMIG consensus statement on the use of the WHO histological classification of thymoma and thymic carcinoma: Refined definitions, histological criteria, and reporting","volume":"9","author":"Marx","year":"2014","journal-title":"J. Thorac. Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1016\/j.athoracsur.2013.04.078","article-title":"Surgical treatment and prognosis of thymic squamous cell carcinoma: A retrospective analysis of 105 cases","volume":"96","author":"Zhao","year":"2013","journal-title":"Ann. Thorac. Surg."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1668","DOI":"10.1016\/j.athoracsur.2012.01.014","article-title":"Thymic carcinoma: Outcomes after surgical resection","volume":"93","author":"Okereke","year":"2012","journal-title":"Ann. Thorac. Surg."},{"key":"ref_7","first-page":"173","article-title":"Thymic neoplasm: A rare disease with a complex clinical presentation","volume":"5","author":"Rashid","year":"2013","journal-title":"J. Thorac. Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1378\/chest.128.1.140","article-title":"Immunohistochemical KIT (CD117) expression in thymic epithelial tumors","volume":"128","author":"Nakagawa","year":"2005","journal-title":"Chest"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1007\/s00428-014-1606-6","article-title":"Thymoma with loss of keratin expression (and giant cells): A potential diagnostic pitfall","volume":"465","author":"Adam","year":"2014","journal-title":"Virchows Arch."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1046\/j.1365-2559.1996.d01-540.x","article-title":"Immunohistochemical localization of Mcl-1 and bcl-2 proteins in thymic epithelial tumours","volume":"29","author":"Chen","year":"1996","journal-title":"Histopathology"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"459","DOI":"10.3892\/ol.2011.267","article-title":"Protein expression status of p53 and epidermal growth factor receptor in thymoma","volume":"2","author":"Cui","year":"2011","journal-title":"Oncol. Lett."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1097\/00000478-199708000-00008","article-title":"Thymic carcinomas, but not thymomas and carcinomas of other sites, show CD5 immunoreactivity","volume":"21","author":"Dorfman","year":"1997","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1048","DOI":"10.1016\/j.prp.2016.09.005","article-title":"Diagnostic roles of MUC1 and GLUT1 in differentiating thymic carcinoma from type B3 thymoma","volume":"212","author":"Du","year":"2016","journal-title":"Pathol. Res. Pract."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"(2009). Comprehensive genomic analysis reveals clinically relevant molecular distinctions between thymic carcinomas and thymomas. Clin. Cancer Res., 15, 6790\u20136799.","DOI":"10.1158\/1078-0432.CCR-09-0644"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1439","DOI":"10.1097\/JTO.0b013e3181e392a8","article-title":"Insulin-like growth factor-1 receptor expression in thymic malignancies","volume":"5","author":"Girard","year":"2010","journal-title":"J. Thorac. Oncol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"9","DOI":"10.3960\/jslrt.53.9","article-title":"The evaluation of immunohistochemical markers and thymic cortical microenvironmental cells in distinguishing thymic carcinoma from type b3 thymoma or lung squamous cell carcinoma","volume":"53","author":"Hayashi","year":"2013","journal-title":"J. Clin. Exp. Hematop."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1007\/s00432-001-0319-9","article-title":"Epidermal growth factor receptor expression in invasive thymoma","volume":"128","author":"Henley","year":"2002","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1361","DOI":"10.1038\/bjc.1997.561","article-title":"High frequency of p53 protein expression in thymic carcinoma but not in thymoma","volume":"76","author":"Hino","year":"1997","journal-title":"Br. J. Cancer"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1002\/(SICI)1097-0215(19971127)73:5<639::AID-IJC5>3.0.CO;2-Y","article-title":"p16INK4, pRB, p53 and cyclin D1 expression and hypermethylation of CDKN2 gene in thymoma and thymic carcinoma","volume":"73","author":"Hirabayashi","year":"1997","journal-title":"Int. J. Cancer"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1326","DOI":"10.1097\/01.MP.0000038463.67854.84","article-title":"Proliferative activity and apoptosis in thymic epithelial neoplasms","volume":"15","author":"Hiroshima","year":"2002","journal-title":"Mod. Pathol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1007\/s00428-011-1041-x","article-title":"MUC1 expression in thymic epithelial tumors: MUC1 may be useful marker as differential diagnosis between type B3 thymoma and thymic carcinoma","volume":"458","author":"Kaira","year":"2011","journal-title":"Virchows Arch."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1111\/j.1365-2613.2010.00745.x","article-title":"Tumour eosinophilia combined with an immunohistochemistry panel is useful in the differentiation of type B3 thymoma from thymic carcinoma","volume":"92","author":"Khoury","year":"2011","journal-title":"Int. J. Exp. Pathol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1093\/ajcp\/109.6.722","article-title":"CD5 labeling of thymic carcinomas and other nonlymphoid neoplasms","volume":"109","author":"Kornstein","year":"1998","journal-title":"Am. J. Clin. Pathol."},{"key":"ref_24","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_25","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.lungcan.2019.03.016","article-title":"High expression level of SOX2 is significantly associated with shorter survival in patients with thymic epithelial tumors","volume":"132","author":"Lee","year":"2019","journal-title":"Lung Cancer"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"4396","DOI":"10.1002\/cncr.26061","article-title":"Steroid receptor expression in thymomas and thymic carcinomas","volume":"117","author":"Mimae","year":"2011","journal-title":"Cancer"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"3129","DOI":"10.1093\/annonc\/mds147","article-title":"Protein expression and gene copy number changes of receptor tyrosine kinase in thymomas and thymic carcinomas","volume":"23","author":"Mimae","year":"2012","journal-title":"Ann. Oncol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1038","DOI":"10.1097\/PAS.0b013e31802b4917","article-title":"Diagnostic utility of thymic epithelial markers CD205 (DEC205) and Foxn1 in thymic epithelial neoplasms","volume":"31","author":"Nonaka","year":"2007","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1007\/s11748-012-0160-x","article-title":"Immunohistochemical analysis of thymic carcinoma focusing on the possibility of molecular targeted and hormonal therapies","volume":"60","author":"Omatsu","year":"2012","journal-title":"Gen. Thorac. Cardiovasc. Surg."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1053\/j.humpath.2003.07.002","article-title":"Expression of calretinin and other mesothelioma-related markers in thymic carcinoma and thymoma","volume":"34","author":"Pan","year":"2003","journal-title":"Hum. Pathol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1447","DOI":"10.1097\/JTO.0b013e3181e96e30","article-title":"Expression and mutational status of c-kit in thymic epithelial tumors","volume":"5","author":"Petrini","year":"2010","journal-title":"J. Thorac. Oncol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/j.lungcan.2017.03.019","article-title":"CD52, CD22, CD26, EG5 and IGF-1R expression in thymic malignancies","volume":"108","author":"Remon","year":"2017","journal-title":"Lung Cancer"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2063","DOI":"10.1002\/ijc.22078","article-title":"COX-2 upregulation in thymomas and thymic carcinomas","volume":"119","author":"Rieker","year":"2006","journal-title":"Int. J. Cancer"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2745","DOI":"10.7314\/APJCP.2012.13.6.2745","article-title":"Diagnostic and clinical significance of KIT(CD117) expression in thymic epithelial tumors in China","volume":"13","author":"Song","year":"2012","journal-title":"Asian Pac. J. Cancer Prev."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1046\/j.1365-2559.1997.5730805.x","article-title":"Expression of p53, mdm2, p21\/waf1 and bcl-2 proteins in thymomas","volume":"30","author":"Stefanaki","year":"1997","journal-title":"Histopathology"},{"key":"ref_36","first-page":"5354","article-title":"Immunohistochemical differentiation between type B3 thymomas and thymic squamous cell carcinomas","volume":"8","author":"Su","year":"2015","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.1507\/endocrj.EJ18-0282","article-title":"Utility of monoclonal PAX8 antibody for distinguishing intrathyroid thymic carcinoma from follicular cell-derived thyroid carcinoma","volume":"65","author":"Suzuki","year":"2018","journal-title":"Endocr. J."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1093\/ajcp\/111.2.235","article-title":"Immunoreactivity of a new CD5 antibody with normal epithelium and malignant tumors including thymic carcinoma","volume":"111","author":"Tateyama","year":"1999","journal-title":"Am. J. Clin. Pathol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.lungcan.2016.09.015","article-title":"Expression of mesothelin in thymic carcinoma and its potential therapeutic significance","volume":"101","author":"Thomas","year":"2016","journal-title":"Lung Cancer"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1016\/j.prp.2015.10.005","article-title":"Glut-1 intensity and pattern of expression in thymic epithelial tumors are predictive of WHO subtypes","volume":"211","author":"Quilhot","year":"2015","journal-title":"Pathol. Res. Pract."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/j.lungcan.2008.03.035","article-title":"Absence of gene mutations in KIT-positive thymic epithelial tumors","volume":"62","author":"Tsuchida","year":"2008","journal-title":"Lung Cancer"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1305","DOI":"10.1097\/PAS.0b013e3182260735","article-title":"Pax8 expression in thymic epithelial neoplasms: An immunohistochemical analysis","volume":"35","author":"Weissferdt","year":"2011","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1296","DOI":"10.1097\/PAS.0b013e3182237f5d","article-title":"Expression of proteasome subunit beta5t in thymic epithelial tumors","volume":"35","author":"Yamada","year":"2011","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"4686","DOI":"10.1002\/cncr.25367","article-title":"Insulin-like growth factor-1 receptor and phosphorylated AKT-serine 473 expression in 132 resected thymomas and thymic carcinomas","volume":"116","author":"Zucali","year":"2010","journal-title":"Cancer"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.1038\/modpathol.2009.105","article-title":"Immunohistochemical differential diagnosis between thymic carcinoma and type B3 thymoma: Diagnostic utility of hypoxic marker, GLUT-1, in thymic epithelial neoplasms","volume":"22","author":"Kojika","year":"2009","journal-title":"Mod. Pathol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1016\/j.prp.2018.01.009","article-title":"An immunohistochemical panel consisting of EZH2, C-KIT, and CD205 is useful for distinguishing thymic squamous cell carcinoma from type B3 thymoma","volume":"214","author":"Kim","year":"2018","journal-title":"Pathol. Res. Pract."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1093\/ajcp\/106.4.483","article-title":"CD5 immunoreactivity of epithelial cells in thymic carcinoma and CASTLE using paraffin-embedded tissue","volume":"106","author":"Berezowski","year":"1996","journal-title":"Am. J. Clin. Pathol."},{"key":"ref_48","first-page":"268","article-title":"CD5 expression in thymic carcinoma","volume":"145","author":"Hishima","year":"1994","journal-title":"Am. J. Pathol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1007\/s00428-013-1371-y","article-title":"Thymic carcinomas: Clinicopathologic study of 37 cases from a single institution","volume":"462","author":"Ghigna","year":"2013","journal-title":"Virchows Arch."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1467","DOI":"10.1097\/JTO.0000000000000017","article-title":"The IASLC\/ITMIG thymic malignancies staging project: Development of a stage classification for thymic malignancies","volume":"8","author":"Detterbeck","year":"2013","journal-title":"J. Thorac. Oncol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"v40","DOI":"10.1093\/annonc\/mdv277","article-title":"Thymic epithelial tumours: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up","volume":"26","author":"Girard","year":"2015","journal-title":"Ann. Oncol."}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/10\/7\/460\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:48:14Z","timestamp":1760176094000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/10\/7\/460"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,7,6]]},"references-count":51,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2020,7]]}},"alternative-id":["diagnostics10070460"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics10070460","relation":{},"ISSN":["2075-4418"],"issn-type":[{"value":"2075-4418","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,7,6]]}}}