Abstract 3327: Epidermal growth factor receptors and penile carcinoma: The role of EGFR and HER2 expression as prognostic and predictive markers
Authors: Silva-Amancio Alice M. T. , Cunha Isabela W. , Guimaraes Gustavo C. , Soares Fernando A. 
Published: May 2015

Abstract
BACKGROUND: Growth factor receptors have recently been described as potential therapeutic targets for penile carcinoma patients, and there are reports on benefits from the clinical use of monoclonal antibodies against EGFR. However, knowledge on the molecular basis of the disease is scarce. For that, we have addressed the expression of EGFR and HER2, as well as mutational and amplification status of EGFR in samples from penile squamous cell carcinoma (PSCC) patients.
METHODS: Clinicopathologic features and survival data from 183 PSCC patients were reviewed from hospital records and immunohistochemistry (IHC) against EGFR and HER2 was performed. Positive cases were those showing strong and complete membrane staining in more than 10% of the tumor cells. HER2 was also classified as positive according to the presence of cytoplasmic staining (cHER2). Sixty cases were submitted to dual-color fluorescence in situ hybridization (FISH) and were classified as unaltered (those harboring 2 signals for each probe) or FISH positive (either if polysomic - harboring more than 2 signals for each probe - or amplified - cases with an EGFR signal:centromeric signal ratio exceeding 2). EGFR exons 18, 19, 20 and 21 from 27 independent frozen cases were sequenced. Variables were compared by the Pearson chi-square or Fisher´s exact test. Survival rates were calculated using the Kaplan-Meier method and compared by log-rank test. Alpha error was set at 5%.
RESULTS: IHC analysis showed that, for EGFR expression, 91 cases (49.7%) were positive and 92 negative, out of which 9 (4,9%) showed no staining at all. Positive cases were associated with higher incidence of recurrence and exophytic growth (p=0.031 and p=0.023, respectively). Membrane staining of HER2 was not seen in any case whereas cHER2 was found in 20.3% (29) of cases, all of them high grade tumors. No low grade tumor presented this staining pattern. cHER2 was also associated with EGFR expression (p=0.017). Regarding FISH, 36 cases were unaltered whereas 32 were FISH positive (out of which 16 presented chromosome 7 polysomy and 6 EGFR amplifications). FISH positivity did not associate with EGFR expression (p=0.403). No mutation in the studied EGFR exons was observed. A polymorphism without clinical significance (p.Q787Q in exon 20) was found in 19/27 cases. cHER2 expression and FISH positivity were an independent risk factor for cancer-specific and overall survival, respectively.
CONCLUSIONS: Success of targeted therapies is highly linked to appropriate patients selection and our findings might indicate that EGFR has a key role in penile carcinogenesis, making PSCC patients potential candidates for EGFR-targeted therapies since both EGFR expression and chromosome 7 polysomy are associated with poor prognosis. A possible interaction between membranous EGFR and cytoplasmic HER2 could favor the use of tyrosine-kinase inhibitors instead of monoclonal antibodies.
Citation Format: Alice M. T. Silva-Amancio, Isabela W. Cunha, Gustavo C. Guimaraes, Fernando A. Soares. Epidermal growth factor receptors and penile carcinoma: The role of EGFR and HER2 expression as prognostic and predictive markers. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3327. doi:10.1158/1538-7445.AM2014-3327