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Purpose  Penile carcinoma is a rare malignant neoplasm with a largely unknown molecular pathogenesis. Telomerase reverse transcriptase promoter ( TERT- p) mutations have been detected in several types of human malignancies. The aim of this study was to investigate the presence of  TERT- p mutations in penile squamous cell carcinomas (SCCs) and their associations with clinicopathologic features.    Methods  In this retrospective study, Sanger sequencing was performed to detect  TERT- p mutations in formalin-fixed paraffin-embedded tissue samples from 37 patients with penile SCC, 16 patients with cutaneous SCC, and 4 patients with non-neoplastic penile/skin tissue. The expression of p16 INK4a  and Ki-67 was investigated via immunohistochemistry. Associations of  TERT-p  mutation with clinicopathological factors, immunohistochemical results, and clinical outcome were statistically analyzed.    Results  Recurrent  TERT-p  mutations were identified in 18 out of 37 (48.6%) penile SCCs, including all 3 carcinoma in situ cases.  TERT-p  mutations were significantly more frequent in non-human papilloma virus (HPV)-related penile SCC types than in non-HPV-related penile SCC based on both histologic classification and p16 INK4a  immunoreactivity. Furthermore,  TERT-p  mutation was associated with a low histologic grade, low mitotic count, absence of necrosis, low Ki-67/MIB-1 labeling index, and absence of lymph node or distant metastasis.    Conclusion  Our study shows  TERT -p mutations are the most frequent somatic mutations in penile SCC. In addition,  TERT -p mutations are far more frequent in non-HPV-related penile SCC than in HPV-related penile SCC, indicating  TERT -p mutations may have a role in tumorigenesis distinct from HPV-related penile SCC.    Supplementary Information  The online version contains supplementary material available at 10.1007/s00432-021-03514-9.

journal of cancer research and clinical oncology

TERT promoter mutations in penile squamous cell carcinoma: high frequency in non-HPV-related type and association with favorable clinicopathologic features