Telomerase reverse transcriptase (TERT) promoter mutation analysis of benign, malignant and reactive urothelial lesions reveals a subpopulation of inverted papilloma with immortalizing genetic change

AIMS: To better understand the genetic ontogeny of inverted papilloma of urinary bladder, we analyzed telomerase reverse transcriptase (TERT) promoter mutation status in a group of 26 inverted papillomas in comparison with the mutation status of urothelial carcinoma with inverted growth (26 cases), conventional urothelial carcinoma (36 Ta noninvasive urothelial carcinoma, 35 T2 invasive urothelial carcinoma), and cystitis glandularis (25 cases). METHODS AND RESULTS: TERT promoter mutations in inverted papilloma, urothelial carcinoma with inverted growth, urothelial carcinoma, and cystitis glandularis were 15% (4/26), 58% (15/26), 63% (45/71), and 0% (0/25), respectively. C228T mutations were the predominant mutations (97%) found in bladder tumors while C250T aberrations occurred in only about 3% of bladder tumors. In the inverted papilloma group, TERT mutation occurred predominantly in female patients (P=0.006). Among urothelial carcinomas, TERT promoter mutation status did not correlate with gender, histologic grade or pathologic stage. CONCLUSIONS: TERT promoter mutations were found in 15% of inverted papillomas. Our data suggest that there is a subpopulation of inverted papilloma that shares a carcinogenetic pathway with urothelial carcinoma with inverted growth and conventional urothelial carcinomas. Caution is warranted in exploring TERT promoter mutation status as a screening or adjunct diagnostic test for bladder cancer. This article is protected by copyright. All rights reserved.