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Clin Genitourin Cancer. 2016 Oct;14(5):450-456.e1. doi: 10.1016/j.clgc.2016.01.013. Epub 2016 Feb 6.

Epidermal Growth Factor Receptor, Excision-Repair Cross-Complementation Group 1 Protein, and Thymidylate Synthase Expression in Penile Cancer.

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USC Keck School of Medicine, Norris Comprehensive Cancer Center, Los Angeles, CA. Electronic address:
USC Keck School of Medicine, Institute of Urology, Los Angeles, CA.
USC Keck School of Medicine, Los Angeles, CA.
All Saints University of Medicine, Chicago, IL.
USC Keck School of Medicine, Norris Comprehensive Cancer Center, Los Angeles, CA.
USC Keck School of Medicine, Department of Pathology, Los Angeles, CA.
Response Genetics, Los Angeles, CA.



To describe the expression of tissue epidermal growth factor receptor (EGFR), excision-repair cross-complementation group 1 protein (ERCC1), and thymidylate synthase (TS) in patients with penile cancer and explore their association with stage and outcome.


A total of 52 patients with penile squamous cell cancer who were treated at the University of Southern California from 1995 to 2010 were identified. Paraffin-embedded tissue underwent mRNA quantitation and immunohistochemistry for expression of EGFR, ERCC1, and TS. KRAS mutations were evaluated using polymerase chain reaction-based sequencing.


EGFR overexpression was common by mRNA (median, 5.09; range, 1.92-104.5) and immunohistochemistry. EGFR expression > 7 was associated with advanced stage and poor differentiation (P = .01 and .034 respectively) but not with survival in multivariate analysis. ERCC1 mRNA expression was a median of 0.65 (range, 0.21-1.87). TS expression was a median of 1.88 (range, 0.54-6.47). ERCC1 and TS expression were not associated with grade, stage, or survival. There were no KRAS mutations identified. A total of 17 men received chemotherapy; 8 (47%) had an objective response, including 1 with a pathologic complete response. There was a trend for lower expression of EGFR corresponding to a higher likelihood of response (response rate [RR]) to chemotherapy: 67% RR in EGFR mRNA < 7 versus 33% RR in EGFR > 7 (P = .31).


High expression of EGFR mRNA in squamous cell carcinoma of the penis is associated with advanced stage and poor differentiation, but not survival. In our small heterogeneous subset, molecular marker expression did not show a correlation with the likelihood of chemotherapy response. A prospective evaluation of the role of the EGFR pathway and its regulatory environment in penile cancer is warranted. Given the rarity of this cancer, collaborative prospective cohort evaluations and trials need to be encouraged.


Chemotherapy response; DNA repair; Growth factor receptor; Squamous cell carcinoma; Targeted therapy

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