Abstract 1165: Evaluation of HPV infection in penile cancer and its association with p16 and MGMT protein expression levels and pathologic variables

Abstract

Abstract INTRODUCTION: Penile carcinoma is an infrequent tumor. However, in developing countries it is a common disease and in specific regions it may represents the most frequent tumor among men. The most important prognostic clinical factor is the presence of lymph node metastasis, which is associated with significant reduced survival to the penile carcinoma patients. Nevertheless, until the present date it was not possible to establish clinical or molecular prognostic markers. Various factors are associated with increased risk for de development of this disease, such as poor hygienic habits, lack of circumcision and HPV infection. HPV DNA can be detected in 20% to 80% of penile squamous cell carcinomas (PSCC). However, the role of HPV on patients’ prognosis is still uncertain. METHODS: We evaluated the frequency of HPV infection in 189 PSCC samples. The presence or absence of HPV DNA was established using generic primers (GP5+/GP6+) specific for the L1 gene of several HPVs. Specimens positive for HPV DNA were genotyped by dot blot hybridization using radioactive probes. We also evaluated the expression levels of the proteins p16 and MGMT through immunohistochemistry. These two proteins show aberrant levels in a wide range of tumors. Protein expression was quantified using an automated image system (ScanScope XT - Aperio), which determined the percentage and intensity of positive cells. The quantification was used to determine if there was loss of expression or normal (positive) expression. RESULTS: HPV infection, characterized by detection of viral DNA on the samples, was observed in 19.6% (37) of the cases. Among the positive HPV samples, 51.3% were infected by HPV16, 21.6% by HPV18 and 2.7% by both HPV16 and 18 concomitantly. The presence of HPV infection was more frequent among tumors with thickness lower than 5mm, suggesting that PSCC with HPV are less aggressive. This finding is in agreement with some studies that showed better prognosis of tumors with HPV infection. The immunohistochemistry assays showed reduced p16 expression in 35.4% (63) and loss of MGMT in 90.1% (146) cases. None association was observed between HPV infection and p16 protein expression. It is well established that the presence of HPV is associated with p16 positive expression. One interesting observation was that MGMT positive expression was associated with positive viral infection. Until this moment, there is no study describing this association in PSCC neither in other tumor types. It was observed an association between p16 reduced levels and poor differentiated tumors, this pathologic variable is associated with bad prognosis. MGMT loss of expression was associated with the presence of lymph node metastasis, suggesting that expression status of this protein can be a molecular marker for PSCC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1165. doi:1538-7445.AM2012-1165