Telomerase reverse transcriptase (TERT) promoter mutations in primary adenocarcinoma of bladder and urothelial carcinoma with glandular differentiation: pathogenesis and diagnostic implications

Telomerase reverse transcriptase (TERT) promoter mutations have been implicated in urothelial carcinogenesis and are present in 60-80% of conventional and variants of urothelial carcinomas. We investigated the prevalence of TERT promoter mutations in 46 cases of bladder nonurachal adenocarcinoma, 30 cases of urothelial carcinoma with glandular differentiation, 24 cases of nephrogenic adenoma, eight cases of villous adenoma, 31 cases of florid cystitis glandularis, and 20 cases of intestinal metaplasia of the bladder. TERT promoter mutations were detected in 33% of adenocarcinomas of urinary bladder and in 67% of urothelial carcinomas with glandular differentiation. All 30 cases of urothelial carcinoma with glandular differentiation harbored identical TERT promoter mutation in both glandular and urothelial carcinoma components from the same tumor, suggesting a common clonal origin. TERT promoter mutations were absent in nephrogenic adenoma, villous adenoma, florid cystitis glandularis, and intestinal metaplasia of the bladder. TERT promoter mutation analysis may be a useful ancillary study in the differential diagnosis.