Paul Giacomo Bruch , Henning Plage , Sebastian Hofbauer , Kira Kornienko , Sarah Weinberger , Florian Roßner , Simon Schallenberg , Martina Kluth , Maximilian Lennartz , Niclas C. Blessin , Andreas H. Marx , Henrik Samtleben , Margit Fisch , Michael Rink , Marcin Slojewski , Krystian Kaczmarek , Thorsten Ecke , Steffen Hallmann , Stefan Koch , Nico Adamini , Sefer Elezkurtaj
{"title":"细胞角蛋白20的表达与晚期(pT4)膀胱尿路上皮癌的分期进展和不良预后有关","authors":"Paul Giacomo Bruch , Henning Plage , Sebastian Hofbauer , Kira Kornienko , Sarah Weinberger , Florian Roßner , Simon Schallenberg , Martina Kluth , Maximilian Lennartz , Niclas C. Blessin , Andreas H. Marx , Henrik Samtleben , Margit Fisch , Michael Rink , Marcin Slojewski , Krystian Kaczmarek , Thorsten Ecke , Steffen Hallmann , Stefan Koch , Nico Adamini , Sefer Elezkurtaj","doi":"10.1016/j.yexmp.2023.104860","DOIUrl":null,"url":null,"abstract":"<div><p>Cytokeratin 20 (CK20) expression is limited to umbrella cells in the normal urothelium. Since CK20 is often upregulated in neoplastic urothelial cells including dysplasia and carcinoma in situ, immunohistochemical CK20 analysis is often used for the assessment of bladder biopsies. CK20 expression is a feature of luminal bladder cancer subtype, but its prognostic relevance is disputed. In this study, we investigated CK20 on >2700 urothelial bladder carcinomas in a tissue microarray format by immunohistochemistry. Cytoplasmic and membranous CK20 staining was seen in 1319 (51.8%) cancers. The fraction of CK20 positive and especially strongly positive cases increased from pTaG2 low grade (44.5% strongly positive) and pTaG2 high grade (57.7%) to pTaG3 high grade (62.3%; <em>p</em> = 0.0006) but was lower in muscle-invasive (pT2–4) carcinomas (51.1% in all pTa vs. 29.6% in pT2–4; <em>p</em> < 0.0001). Within pT2–4 carcinomas, CK20 positivity was linked to nodal metastasis and lymphatic vessel invasion (p < 0.0001 each) and to venous invasion (<em>p</em> = 0.0177). CK20 staining was unrelated to overall patient survival if all 605 pT2–4 carcinomas were jointly analyzed but subgroup analyses revealed a significant association of CK20 positivity with favorable prognosis in 129 pT4 carcinomas (<em>p</em> = 0.0005). CK20 positivity was strongly linked to the expression of GATA3 (<em>p</em> < 0.0001), another feature of luminal bladder cancer. The combined analysis of both parameters showed best prognosis for luminal A (CK20+/GATA3+, CK20+/GATA3-) and worst outcome for luminal B (CK20−/GATA3+) and basal/squamous (CK20−/GATA3-) in pT4 urothelial carcinomas (<em>p</em> = 0.0005). In summary, the results of our study demonstrate a complex role of CK20 expression in urothelial neoplasms including neoexpression in pTa tumors, a subsequent loss of CK20 expression in a subset of tumors progressing to muscle-invasion, and a stage dependent prognostic role in muscle-invasive cancers.</p></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"131 ","pages":"Article 104860"},"PeriodicalIF":2.8000,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"2","resultStr":"{\"title\":\"Cytokeratin 20 expression is linked to stage progression and to poor prognosis in advanced (pT4) urothelial carcinoma of the bladder\",\"authors\":\"Paul Giacomo Bruch , Henning Plage , Sebastian Hofbauer , Kira Kornienko , Sarah Weinberger , Florian Roßner , Simon Schallenberg , Martina Kluth , Maximilian Lennartz , Niclas C. Blessin , Andreas H. Marx , Henrik Samtleben , Margit Fisch , Michael Rink , Marcin Slojewski , Krystian Kaczmarek , Thorsten Ecke , Steffen Hallmann , Stefan Koch , Nico Adamini , Sefer Elezkurtaj\",\"doi\":\"10.1016/j.yexmp.2023.104860\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Cytokeratin 20 (CK20) expression is limited to umbrella cells in the normal urothelium. Since CK20 is often upregulated in neoplastic urothelial cells including dysplasia and carcinoma in situ, immunohistochemical CK20 analysis is often used for the assessment of bladder biopsies. CK20 expression is a feature of luminal bladder cancer subtype, but its prognostic relevance is disputed. In this study, we investigated CK20 on >2700 urothelial bladder carcinomas in a tissue microarray format by immunohistochemistry. Cytoplasmic and membranous CK20 staining was seen in 1319 (51.8%) cancers. The fraction of CK20 positive and especially strongly positive cases increased from pTaG2 low grade (44.5% strongly positive) and pTaG2 high grade (57.7%) to pTaG3 high grade (62.3%; <em>p</em> = 0.0006) but was lower in muscle-invasive (pT2–4) carcinomas (51.1% in all pTa vs. 29.6% in pT2–4; <em>p</em> < 0.0001). Within pT2–4 carcinomas, CK20 positivity was linked to nodal metastasis and lymphatic vessel invasion (p < 0.0001 each) and to venous invasion (<em>p</em> = 0.0177). CK20 staining was unrelated to overall patient survival if all 605 pT2–4 carcinomas were jointly analyzed but subgroup analyses revealed a significant association of CK20 positivity with favorable prognosis in 129 pT4 carcinomas (<em>p</em> = 0.0005). CK20 positivity was strongly linked to the expression of GATA3 (<em>p</em> < 0.0001), another feature of luminal bladder cancer. The combined analysis of both parameters showed best prognosis for luminal A (CK20+/GATA3+, CK20+/GATA3-) and worst outcome for luminal B (CK20−/GATA3+) and basal/squamous (CK20−/GATA3-) in pT4 urothelial carcinomas (<em>p</em> = 0.0005). In summary, the results of our study demonstrate a complex role of CK20 expression in urothelial neoplasms including neoexpression in pTa tumors, a subsequent loss of CK20 expression in a subset of tumors progressing to muscle-invasion, and a stage dependent prognostic role in muscle-invasive cancers.</p></div>\",\"PeriodicalId\":12176,\"journal\":{\"name\":\"Experimental and molecular pathology\",\"volume\":\"131 \",\"pages\":\"Article 104860\"},\"PeriodicalIF\":2.8000,\"publicationDate\":\"2023-06-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"2\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Experimental and molecular pathology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0014480023000114\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"PATHOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Experimental and molecular pathology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0014480023000114","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"PATHOLOGY","Score":null,"Total":0}
Cytokeratin 20 expression is linked to stage progression and to poor prognosis in advanced (pT4) urothelial carcinoma of the bladder
Cytokeratin 20 (CK20) expression is limited to umbrella cells in the normal urothelium. Since CK20 is often upregulated in neoplastic urothelial cells including dysplasia and carcinoma in situ, immunohistochemical CK20 analysis is often used for the assessment of bladder biopsies. CK20 expression is a feature of luminal bladder cancer subtype, but its prognostic relevance is disputed. In this study, we investigated CK20 on >2700 urothelial bladder carcinomas in a tissue microarray format by immunohistochemistry. Cytoplasmic and membranous CK20 staining was seen in 1319 (51.8%) cancers. The fraction of CK20 positive and especially strongly positive cases increased from pTaG2 low grade (44.5% strongly positive) and pTaG2 high grade (57.7%) to pTaG3 high grade (62.3%; p = 0.0006) but was lower in muscle-invasive (pT2–4) carcinomas (51.1% in all pTa vs. 29.6% in pT2–4; p < 0.0001). Within pT2–4 carcinomas, CK20 positivity was linked to nodal metastasis and lymphatic vessel invasion (p < 0.0001 each) and to venous invasion (p = 0.0177). CK20 staining was unrelated to overall patient survival if all 605 pT2–4 carcinomas were jointly analyzed but subgroup analyses revealed a significant association of CK20 positivity with favorable prognosis in 129 pT4 carcinomas (p = 0.0005). CK20 positivity was strongly linked to the expression of GATA3 (p < 0.0001), another feature of luminal bladder cancer. The combined analysis of both parameters showed best prognosis for luminal A (CK20+/GATA3+, CK20+/GATA3-) and worst outcome for luminal B (CK20−/GATA3+) and basal/squamous (CK20−/GATA3-) in pT4 urothelial carcinomas (p = 0.0005). In summary, the results of our study demonstrate a complex role of CK20 expression in urothelial neoplasms including neoexpression in pTa tumors, a subsequent loss of CK20 expression in a subset of tumors progressing to muscle-invasion, and a stage dependent prognostic role in muscle-invasive cancers.
期刊介绍：
Under new editorial leadership, Experimental and Molecular Pathology presents original articles on disease processes in relation to structural and biochemical alterations in mammalian tissues and fluids and on the application of newer techniques of molecular biology to problems of pathology in humans and other animals. The journal also publishes selected interpretive synthesis reviews by bench level investigators working at the "cutting edge" of contemporary research in pathology. In addition, special thematic issues present original research reports that unravel some of Nature''s most jealously guarded secrets on the pathologic basis of disease.
Research Areas include: Stem cells; Neoangiogenesis; Molecular diagnostics; Polymerase chain reaction; In situ hybridization; DNA sequencing; Cell receptors; Carcinogenesis; Pathobiology of neoplasia; Complex infectious diseases; Transplantation; Cytokines; Flow cytomeric analysis; Inflammation; Cellular injury; Immunology and hypersensitivity; Athersclerosis.
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