Telomerase Reverse Transcriptase (TERT) Promoter Mutation Analysis of Benign, Malignant and Reactive Urothelial Lesions Reveals a Subpopulation of Inverted Papilloma with Immortalizing Genetic Change

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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.

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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

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