KDM6A expression loss is frequent in low grade non-invasive urothelial carcinomas of the urinary bladder.
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Viehweger Florian, Gorbokon Natalia, Büyücek Seyma, Plage Henning, Hofbauer Sebastian, Furlano Kira, Weinberger Sarah, Ralla Bernhard, Fendler Annika, Biernath Nadine, Erber Barbara, Roßner Florian, Schallenberg Simon, Elezkurtaj Sefer, Lennartz Maximilian, Bady Elena, Hube-Magg Claudia, Marx Andreas H, Samtleben Henrik, Fisch Margit, Rink Michael, Zecha Henrik, Slojewski Marcin, Kaczmarek Krystian, Ecke Thorsten, Koch Stefan, Adamini Nico, Simon Ronald, Sauter Guido, Weischenfeldt Joachim, Klatte Tobias, Schlomm Thorsten, Horst David, Kluth Martina, Minner Sarah
Аннотация
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.