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.
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 p16INK4a and Ki-67 was investigated via immunohistochemistry. Associations of TERT-p mutation with clinicopathological factors, immunohistochemical results, and clinical outcome were statistically analyzed.
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 p16INK4a 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.
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.
Journal of cancer research and clinical oncology. 2021 Feb 26 [Epub ahead of print]
Sang Kyum Kim, Jang-Hee Kim, Jae Ho Han, Nam Hoon Cho, Se Joong Kim, Sun Il Kim, Seol Ho Choo, Ji Su Kim, Bumhee Park, Ji Eun Kwon
Department of Pathology, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea., Department of Pathology, Ajou University School of Medicine, 164, Worldcup-ro, Yeongtong-gu, Suwon, 16499, Republic of Korea., Department of Urology, Ajou University School of Medicine, Suwon, Republic of Korea., Office of Biostatistics, Medical Research Collaborating Center, Ajou Research Institute for Innovation, Ajou University Medical Center, Suwon, Republic of Korea., Department of Pathology, Ajou University School of Medicine, 164, Worldcup-ro, Yeongtong-gu, Suwon, 16499, Republic of Korea. .