title: Epidermal Growth Factor Receptor, Excision-Repair Cross-Complementation Group 1 Protein, and Thymidylate Synthase Expression in Penile Cancer.
abstract: 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.
authors.affiliation: USC Keck School of Medicine, Norris Comprehensive Cancer Center, Los Angeles, CA. Electronic address: dorff@usc.edu.
authors.forename: Tanya B
authors.initials: TB
authors.lastname: Dorff
authors.affiliation: USC Keck School of Medicine, Institute of Urology, Los Angeles, CA.
authors.forename: Anne K
authors.initials: AK
authors.lastname: Schuckman
authors.affiliation: USC Keck School of Medicine, Los Angeles, CA.
authors.forename: Rachel
authors.initials: R
authors.lastname: Schwartz
authors.affiliation: All Saints University of Medicine, Chicago, IL.
authors.forename: Sadaf
authors.initials: S
authors.lastname: Rashad
authors.affiliation: USC Keck School of Medicine, Los Angeles, CA.
authors.forename: Ajaz
authors.initials: A
authors.lastname: Bulbul
authors.affiliation: USC Keck School of Medicine, Institute of Urology, Los Angeles, CA.
authors.forename: Jie
authors.initials: J
authors.lastname: Cai
authors.affiliation: USC Keck School of Medicine, Norris Comprehensive Cancer Center, Los Angeles, CA.
authors.forename: Jacek
authors.initials: J
authors.lastname: Pinski
authors.affiliation: USC Keck School of Medicine, Department of Pathology, Los Angeles, CA.
authors.forename: Yanling
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Response Genetics, Los Angeles, CA.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Danenberg
authors.affiliation: USC Keck School of Medicine, Institute of Urology, Los Angeles, CA.
authors.forename: Eila
authors.initials: E
authors.lastname: Skinner
authors.affiliation: USC Keck School of Medicine, Norris Comprehensive Cancer Center, Los Angeles, CA.
authors.forename: David I
authors.initials: DI
authors.lastname: Quinn
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D004720:Endonucleases / Q000235:genetics* / Q000378:metabolism; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D010412:Penile Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D011446:Prospective Studies; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D016019:Survival Analysis; D013940:Thymidylate Synthase / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D004268:DNA-Binding Proteins; C117307:KRAS protein, human; D013940:Thymidylate Synthase; C512478:EGFR protein, human; D066246:ErbB Receptors; C071447:ERCC1 protein, human; D004720:Endonucleases; D016283:Proto-Oncogene Proteins p21(ras)
keywords: Chemotherapy response; DNA repair; Growth factor receptor; Squamous cell carcinoma; Targeted therapy