Abstract 5577: HER2 cytoplasmic staining and penile cancer

Abstract

BACKGROUND: Although rare in developed regions, penile carcinoma is a serious concern for undeveloped countries such as Brazil, where it can represent up to 10% of all malignancies. HER2 is a well-known growth factor membrane receptor that has its expression level usually associated with aggressive disease. Recently, some studies have shown that soluble fractions of HER2 intracellular domain are found in tumors cytoplasm and they still activate intracellular pathways related to cell proliferation and survival. MATERIAL AND METHODS: Immunohistochemistry against HER2 was carried out in 195 penile carcinoma samples selected from the files of AC Camargo Hospital, Brazil, using the monoclonal CB11 antibody (Novocastra™), which recognizes specifically HER2 intracellular domain. Cases were classified as positive or negative according to membrane and to cytoplasmic staining. All statistical analyses were performed by the SPSS for Windows 18.0, SPSS Inc. Comparison between category variables was performed by the Pearson chi-square test or the Fisher's exact test. Survival rates were calculated using the Kaplan-Meier method and the curves were compared by means of the log-rank test. In all statistical tests, the alpha error was set at 5%. RESULTS: None of the cases showed membrane staining for HER2. However, a clear and strong cytoplasm staining was observed in 28 cases (14,9%), as shown in figure 1. The staining was limited to the tumor cells and does not represent background or artifact. Univariate analyses showed that overexpression is associated with higher histologic grade (p <0,001) and lower overall survival (p=0,007). Multivariate analyses showed that HER2 in the cytoplasm is an independent risk factor for death (RR=2,966; IC 95% [1,6-5,2]; p <0,001). CONCLUSIONS: Corroborating with recent findings that cytoplasmic fragments of HER2 can be active kinases, the present study suggests that the presence of HER2 in tumor cytoplasm is a prognostic marker in penile carcinoma. We have also demonstrated that, although no membrane staining was seen, presence of HER2 in cytoplasm is an independent risk factor for death in this neoplasm. 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 5577. doi:1538-7445.AM2012-5577