Telomere shortening distinguishes inverted urothelial neoplasms

Aims To investigate relative telomere length in inverted urothelial neoplasms, including inverted papilloma and urothelial carcinoma with an inverted growth pattern. Telomere shortening has been implicated as an early event in the development of epithelial malignancies in a number of organ systems. Methods and results Formalin-fixed, paraffin-embedded tissue sections from 77 cases were studied, including 26 cases of inverted papilloma, 26 urothelial carcinomas with inverted growth, and 25 cases of cystitis glandularis. Quantitative fluorescence in-situ hybridization (FISH) was performed on interphase nuclei, utilizing a telomere-specific peptide nucleic acid probe to assess telomeric signal intensity. Relative telomere lengths for urothelial carcinoma with inverted growth, cystitis glandularis and inverted papilloma were 29%, 84%, and 91%, respectively. A statistically significant reduction in relative telomere length was present between urothelial carcinoma with inverted growth and inverted papilloma (P<0.001); no significant difference was detected between normal urothelium, cystitis glandularis, and inverted papilloma. Conclusions Significant telomere shortening in urothelial carcinoma with inverted growth as compared with inverted papilloma distinguishes the two lesions, and supports the notion that inverted papilloma is a benign neoplasm with a distinct pathogenetic mechanism of development. Telomeric FISH analysis may be a useful biomarker in distinguishing inverted papilloma from urothelial carcinoma with inverted growth.