Florian Viehweger, Natalia Gorbokon, Seyma Büyücek, Henning Plage, Sebastian Hofbauer, Kira Furlano, Sarah Weinberger, Bernhard Ralla, Annika Fendler, Nadine Biernath, Barbara Erber, Florian Roßner, Simon Schallenberg, Sefer Elezkurtaj, Maximilian Lennartz, Elena Bady, Claudia Hube-Magg, Andreas H Marx, Henrik Samtleben, Margit Fisch, Michael Rink, Henrik Zecha, Marcin Slojewski, Krystian Kaczmarek, Thorsten Ecke, Stefan Koch, Nico Adamini, Ronald Simon, Guido Sauter, Joachim Weischenfeldt, Tobias Klatte, Thorsten Schlomm, David Horst, Martina Kluth, Sarah Minner
{"title":"KDM6A表达缺失在低级别非侵袭性膀胱尿路上皮癌中很常见。","authors":"Florian Viehweger, Natalia Gorbokon, Seyma Büyücek, Henning Plage, Sebastian Hofbauer, Kira Furlano, Sarah Weinberger, Bernhard Ralla, Annika Fendler, Nadine Biernath, Barbara Erber, Florian Roßner, Simon Schallenberg, Sefer Elezkurtaj, Maximilian Lennartz, Elena Bady, Claudia Hube-Magg, Andreas H Marx, Henrik Samtleben, Margit Fisch, Michael Rink, Henrik Zecha, Marcin Slojewski, Krystian Kaczmarek, Thorsten Ecke, Stefan Koch, Nico Adamini, Ronald Simon, Guido Sauter, Joachim Weischenfeldt, Tobias Klatte, Thorsten Schlomm, David Horst, Martina Kluth, Sarah Minner","doi":"10.32074/1591-951X-1104","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>The gene lysine demethylase 6A (<i>KDM6A</i>) located on chromosome Xp11 often shows truncating mutations in urothelial carcinoma. Mutations resulting in protein expression loss can be detected by immunohistochemistry (IHC).</p><p><strong>Methods: </strong>A tissue microarray with >2,500 bladder tumors was analyzed by IHC. 78 cancers were sequenced for KDM6A.</p><p><strong>Results: </strong>KDM6A expression loss decreased from 36% of 345 pTaG2 low-grade to 23% of 152 pTaG2 high-grade and 18.5% of 92 pTaG3 tumors (p=0.0004) but not further in pT2-4 cancers (17.2-21.9%). KDM6A staining was unrelated to pT, pN, grade, and overall survival (p>0.1894) in 636 patients with pT2-4 cancers. KDM6A loss was more common in male (22.2%) than in female patients (15.4%; p=0.0067), and in tumors from males with Y-chromosome loss (36.1%) than without Y-loss (16.3%; p<0.0001). A KDM6A loss occurred in all 15 male and in 17 (74%) of 23 female patients with a truncating KDM6A mutation, but only 15 (75%) of 20 male and 17 (81%) of 21 female patients with KDM6A expression loss had a truncating mutation.</p><p><strong>Conclusions: </strong>KDM6A expression loss is frequent in urothelial carcinoma and mostly due to truncating mutations. KDM6A IHC may be a useful tool for the distinction of neoplastic from non-neoplastic urothelial cells in follow-up examinations of patients with KDM6A deficient cancers.</p>","PeriodicalId":45893,"journal":{"name":"PATHOLOGICA","volume":"117 3","pages":"296-305"},"PeriodicalIF":2.9000,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12236142/pdf/","citationCount":"0","resultStr":"{\"title\":\"KDM6A expression loss is frequent in low grade non-invasive urothelial carcinomas of the urinary bladder.\",\"authors\":\"Florian Viehweger, Natalia Gorbokon, Seyma Büyücek, Henning Plage, Sebastian Hofbauer, Kira Furlano, Sarah Weinberger, Bernhard Ralla, Annika Fendler, Nadine Biernath, Barbara Erber, Florian Roßner, Simon Schallenberg, Sefer Elezkurtaj, Maximilian Lennartz, Elena Bady, Claudia Hube-Magg, Andreas H Marx, Henrik Samtleben, Margit Fisch, Michael Rink, Henrik Zecha, Marcin Slojewski, Krystian Kaczmarek, Thorsten Ecke, Stefan Koch, Nico Adamini, Ronald Simon, Guido Sauter, Joachim Weischenfeldt, Tobias Klatte, Thorsten Schlomm, David Horst, Martina Kluth, Sarah Minner\",\"doi\":\"10.32074/1591-951X-1104\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objective: </strong>The gene lysine demethylase 6A (<i>KDM6A</i>) located on chromosome Xp11 often shows truncating mutations in urothelial carcinoma. Mutations resulting in protein expression loss can be detected by immunohistochemistry (IHC).</p><p><strong>Methods: </strong>A tissue microarray with >2,500 bladder tumors was analyzed by IHC. 78 cancers were sequenced for KDM6A.</p><p><strong>Results: </strong>KDM6A expression loss decreased from 36% of 345 pTaG2 low-grade to 23% of 152 pTaG2 high-grade and 18.5% of 92 pTaG3 tumors (p=0.0004) but not further in pT2-4 cancers (17.2-21.9%). KDM6A staining was unrelated to pT, pN, grade, and overall survival (p>0.1894) in 636 patients with pT2-4 cancers. KDM6A loss was more common in male (22.2%) than in female patients (15.4%; p=0.0067), and in tumors from males with Y-chromosome loss (36.1%) than without Y-loss (16.3%; p<0.0001). A KDM6A loss occurred in all 15 male and in 17 (74%) of 23 female patients with a truncating KDM6A mutation, but only 15 (75%) of 20 male and 17 (81%) of 21 female patients with KDM6A expression loss had a truncating mutation.</p><p><strong>Conclusions: </strong>KDM6A expression loss is frequent in urothelial carcinoma and mostly due to truncating mutations. KDM6A IHC may be a useful tool for the distinction of neoplastic from non-neoplastic urothelial cells in follow-up examinations of patients with KDM6A deficient cancers.</p>\",\"PeriodicalId\":45893,\"journal\":{\"name\":\"PATHOLOGICA\",\"volume\":\"117 3\",\"pages\":\"296-305\"},\"PeriodicalIF\":2.9000,\"publicationDate\":\"2025-06-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12236142/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"PATHOLOGICA\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.32074/1591-951X-1104\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"PATHOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"PATHOLOGICA","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.32074/1591-951X-1104","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PATHOLOGY","Score":null,"Total":0}
KDM6A expression loss is frequent in low grade non-invasive urothelial carcinomas of the urinary bladder.
Objective: The gene lysine demethylase 6A (KDM6A) located on chromosome Xp11 often shows truncating mutations in urothelial carcinoma. Mutations resulting in protein expression loss can be detected by immunohistochemistry (IHC).
Methods: A tissue microarray with >2,500 bladder tumors was analyzed by IHC. 78 cancers were sequenced for KDM6A.
Results: KDM6A expression loss decreased from 36% of 345 pTaG2 low-grade to 23% of 152 pTaG2 high-grade and 18.5% of 92 pTaG3 tumors (p=0.0004) but not further in pT2-4 cancers (17.2-21.9%). KDM6A staining was unrelated to pT, pN, grade, and overall survival (p>0.1894) in 636 patients with pT2-4 cancers. KDM6A loss was more common in male (22.2%) than in female patients (15.4%; p=0.0067), and in tumors from males with Y-chromosome loss (36.1%) than without Y-loss (16.3%; p<0.0001). A KDM6A loss occurred in all 15 male and in 17 (74%) of 23 female patients with a truncating KDM6A mutation, but only 15 (75%) of 20 male and 17 (81%) of 21 female patients with KDM6A expression loss had a truncating mutation.
Conclusions: KDM6A expression loss is frequent in urothelial carcinoma and mostly due to truncating mutations. KDM6A IHC may be a useful tool for the distinction of neoplastic from non-neoplastic urothelial cells in follow-up examinations of patients with KDM6A deficient cancers.
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