Abstract 4827: Gene copy number and protein expression of growth factor receptors EGFR and HER2 and their prognostic potential in penile squamous cell carcinoma
Authors: Silva-Amancio Alice M. , Neves Jose I. , Cunha Isabela W. , da Costa Walter , Guimarães Gustavo C. , Soares Fernando A. 
Published: August 2015

BACKGROUND: Penile squamous cell carcinoma (PSCC) is a disease typical of less developed regions of the globe, and its molecular mechanisms are not clearly understood. Novel EGFR-targeted therapies have arisen as a potential treatment alternative and, although the mechanisms of EGFR activation in PSCC are unknown. For that, we have addressed the protein expression and gene copy number (CGN) of EGFR and HER2 in a large cohort of PSCC patients.

METHODS: Immunohistochemistry (IHC) against EGFR and HER2 was performed in samples from 183 PSCC patients using the biotin-free polymer method. Overexpressing cases were those showing strong and complete membrane staining in more than 10% of the tumor cells. Seventy-three cases were submitted to dual color fluorescence in situ hybridization (FISH) for evaluation of GCN of both genes (and their respective centromere) and were classified as disomy (2 signals of the gene and chromosome centromere in each nucleus), polysomy (more than 2 signals of the gene and centromere), or gene gains (cases with a gene signal:centromeric signal ratio exceeding 2).

RESULTS: Regarding EGFR, almost half of cases (91, or 49.7%) overexpressed the marker, 81 (54.5%) presented low expression, and 9 (4.9%) showed no staining at all. Overexpression associated with presence of recurrence (p = 0.031). Most cases presented disomy of chromosome 7 (46/68, or 67.6%), 16 cases (23.5%) were polysomies, and 6 cases (9.9%) EGFR gains (up to 6 copies of the gene x 2 signals of chromosome 7 centromere). Increased EGFR copies due to polysomy or amplification was associated with higher histologic grade and shorter cancer-specific survival (p = 0.008 and p = 0.019, respectively) but not with protein overexpression (p = 0.403). No membrane expression of HER2 was seen, but a cytoplasmic staining was found in 214.9% (28) of cases, all of them high grade tumors. Cytoplasmic HER2 (cHER2) associated with EGFR overexpression (p = 0.017), and reduced cancer-specific survival (p = 0.014). No amplifications of HER2 were seen, but chromosome 17 polysomy was present in 16 (21.9%) of 73 valid cases. Cases presenting polysomy of chromosome 17 (P17) presented recurrence (p = 0.008), higher histological grade tumors (p = 0.030) and perineural invasion (p = 0.045) more frequently. Cancer-specific survival of P17 patients was also shorter (p = 0.014).

CONCLUSIONS: Our results suggest a possible prognostic role for EGFR overexpression and HER2 cytoplasmic staining, stratifying patients at increased risk of disease recurrence or death. GCN analysis of the studied genes showed that increased EGFR gene copies is a strong predictor of cancer death, as well as polysomy of chromosome 17 is. We believe an important unbalance in chromosome number might explain the poor outcome seen in patients.

Funding: Capes and FAPESP.

Note: This abstract was not presented at the meeting.

Citation Format: Alice M. Silva-Amancio, Jose I. Neves, Isabela W. Cunha, Walter da Costa, Gustavo C. Guimarães, Fernando A. Soares. Gene copy number and protein expression of growth factor receptors EGFR and HER2 and their prognostic potential in penile squamous cell carcinoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4827. doi:10.1158/1538-7445.AM2015-4827