Telomerase Reverse Transcriptase (TERT) Promoter Mutation Analysis of Benign, Malignant and Reactive Urothelial Lesions Reveals a Subpopulation of Inverted Papilloma with Immortalizing Genetic Change
Cheng L, Davidson DD, Wang M, Lopez-Beltran A, Montironi R, Wang L, Tan PH, MacLennan GT, Williamson SR, and Zhang S. Telomerase reverse transcriptase (TERT) promoter mutation analysis of benign, malignant and reactive urothelial lesions reveals a subpopulation of inverted papilloma with immortalizing genetic change. Histopathology 2015.
AIMS: To understand more clearly the genetic ontogeny of inverted papilloma of urinary bladder, we analysed 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 non-invasive 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 found in 15% (four of 26), 58% (15 of 26), 63% (45 of 71) and 0% (none of 25), respectively. C228T mutations were the predominant mutations (97%) found in bladder tumours, while C250T aberrations occurred in approximately 3% of bladder tumours. 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, histological grade or pathological 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.
Medical Subject Headings
Aged; Aged, 80 and over; Carcinoma; Cohort Studies; Cystitis; DNA Mutational Analysis; Female; Humans; Male; Middle Aged; Mutation; Papilloma, Inverted; Promoter Regions, Genetic; Telomerase; Urinary Bladder; Urinary Bladder Neoplasms; Urothelium