MYC copy number gains are associated with poor outcome in penile squamous cell carcinoma

Abstract

Purpose: We determined MYC gene numerical aberrations and protein expression at different stages of penile squamous cell carcinoma carcinogenesis. We correlated these findings with clinicopathological parameters and HPV infection.

Materials and methods: We evaluated 79 cases of penile squamous cell carcinoma, including 11 in situ and 68 invasive carcinomas. The MYC cytogenetic profile was evaluated by fluorescence in situ hybridization. HPV was detected by polymerase chain reaction amplification.

Results: MYC gains were identified in 4 of 11 in situ carcinomas (36%) and 50 of 68 invasive penile squamous cell carcinomas (73%). A significant association between MYC gains, and tumor progression and poor outcome was demonstrated (p <0.05). HPV DNA was detected in 32 of 79 penile squamous cell carcinomas (39%). High risk type 16 was the most prevalent type. MYC numerical aberrations did not correlate with HPV status. A significant association between HPV and MYC protein over expression was noted. In HPV negative cases MYC gains correlated with MYC over expression.

Conclusions: MYC gains progressively increased during penile squamous cell carcinoma progression from in situ samples to metastases. MYC gains were an independent factor for poor prognosis. These findings were independent of HPV infection. MYC expression was increased in samples with HPV infection, probably reflecting direct activation of MYC.