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
Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Department of Urology, Charité, Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.
Pathologica. 2025 Jun;117(3):296-305. doi: 10.32074/1591-951X-1104.
The gene lysine demethylase 6A () located on chromosome Xp11 often shows truncating mutations in urothelial carcinoma. Mutations resulting in protein expression loss can be detected by immunohistochemistry (IHC).
A tissue microarray with >2,500 bladder tumors was analyzed by IHC. 78 cancers were sequenced for KDM6A.
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.
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.
位于Xp11染色体上的赖氨酸去甲基化酶6A（KDM6A）基因在尿路上皮癌中常显示截短突变。可通过免疫组织化学（IHC）检测导致蛋白质表达缺失的突变。
采用IHC分析包含2500多个膀胱肿瘤的组织芯片。对78例癌症进行KDM6A测序。
KDM6A表达缺失率从345例pTaG2低级别肿瘤中的36%降至152例pTaG2高级别肿瘤中的23%以及92例pTaG3肿瘤中的18.5%（p = 0.0004），但在pT2 - 4期癌症中（17.2 - 21.9%）未进一步降低。在636例pT2 - 4期癌症患者中，KDM6A染色与pT、pN、分级及总生存期均无关（p > 0.1894）。KDM6A缺失在男性患者（22.2%）中比女性患者（15.4%；p = 0.0067）更常见，在伴有Y染色体缺失的男性肿瘤中（36.1%）比无Y染色体缺失的男性肿瘤中（16.3%；p < 0.0001）更常见。在所有15例男性和23例女性中有截短KDM6A突变的患者中，17例（74%）出现KDM6A缺失，但在KDM6A表达缺失的20例男性患者中仅15例（75%）以及21例女性患者中17例（81%）有截短突变。
KDM6A表达缺失在尿路上皮癌中很常见，且主要归因于截短突变。在对KDM6A缺陷型癌症患者的随访检查中，KDM6A免疫组化可能是区分肿瘤性与非肿瘤性尿路上皮细胞的有用工具。
