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

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).

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.

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.

Histopathology. 2015 Dec 18 [Epub ahead of print]

Liang Cheng, Darrell D Davidson, Mingsheng Wang, Antonio Lopez-Beltran, Rodolfo Montironi, Lisha Wang, Puay-Hoon Tan, Gregory T MacLennan, Sean R Williamson, Shaobo Zhang

Departments of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA. , Departments of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA. , Departments of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA. , Department of Pathology,Unit of Anatomical Pathology, Department of Surgery, Faculty of Medicine, Cordoba, Spain and Champalimaud Clinical Center, Lisbon, Portugal. , Institute of Pathological Anatomy and Histopathology, School of Medicine, Polytechnic University of the Marche Region (Ancona), United Hospitals, Ancona, Italy. , Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China. , Department of Pathology, Singapore General Hospital, Singapore. , Department of Pathology, Case Western Reserve University, Cleveland, OH, USA. , Department of Pathology and Laboratory Medicine, Henry Ford Health System, Detroit, MI, USA. , Departments of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.

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