Biological Significance of TERT Promoter Mutation in Papillary Urothelial Neoplasm of Low Malignant Potential

Abstract

Aims

Mutations in FGFR3 and the promoter region of the telomerase reverse transcriptase (TERT) gene have been frequently found in urothelial carcinoma of the urinary bladder. However, related data for papillary urothelial neoplasm of low malignant potential (PUNLMP) are limited. In this study, we investigated the mutation status of the TERT promoter, FGFR3 gene, and HRAS gene in low-grade papillary urothelial neoplasms and evaluated their prognostic significance.

Methods and Results

The cases included in this study comprised 21 inverted papillomas, 30 PUNLMPs, and 34 low-grade noninvasive papillary urothelial carcinomas (NIPUCs). TERT promoter mutations were observed in 10 (33%) PUNLMPs and 17 (50%) low-grade NIPUCs, but not in any inverted papilloma. FGFR3 mutations were more frequently observed in PUNLMP and low-grade NIPUC than in inverted papillomas (P = .009), whereas the opposite trend was noted for HRAS mutations (P < .001). Regarding the clinical outcome, TERT promoter mutation was associated with a higher recurrence rate in PUNLMP (P = .024) but not in low-grade NIPUC (P = .530). Notably, PUNLMP cases with TERT promoter mutations had a similar recurrence rate to that in low-grade NIPUC cases (P = .487).

Conclusions

Our results suggest that the status of the TERT promoter mutation may serve as a biomarker of prognostic stratification in patients with PUNLMP.

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