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

Document Type

Article

Publication Date

7-1-2016

Publication Title

Histopathology

Keywords

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

Abstract

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

PubMed ID

26679899

Volume

69

Issue

1

First Page

107

Last Page

113

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