EGFR, TS, and ERCC1 expression in penile squamous cancer (PSC).

Abstract

219 Background: PSC is an aggressive disease with devastating consequences. While near-universal EGFR overexpression has been documented, little is known about its clinical implications, and the potential role of KRAS mutations has not been described. In other tumor types, ERCC1 and TS expression are associated with response to platinum and 5FU chemotherapy, but have not yet been evaluated in PSC. Methods: After IRB approval, 28 PSC patients treated at LAC-USC were identified with tumor specimens available. Testing for EGFR, TS, and ERCC1 expression relative to internal standard gene was performed by real-time RT-PCR and correlated with clinical features. Results: The median age was 45 (30-78). There were 2 Black, 1 Asian, 1 White, and 15 Hispanic men; 9 had unspecified race. T stages included 4 Tis, 6 T1, 17 T2, and 9 T3; 11 men had lymph node (LN) involvement. No KRAS mutations were identified. EGFR had the highest relative expression (median 4.65, range 1.6-44.2), followed by TS (median 1.69, range 0.49-4.69); ERCC1 overexpression was rare (median 0.54, range 0.21-1.29). Higher EGFR expression was significantly associated with poor differentiation (median 12.5 compared to 3.6 for moderate/well differentiated tumors) on continuous (p=0.03 by Mann Whitney) and cut-point analysis using >7 (two- sided p=0.03 by Fisher's exact test) but did not correlate with stage. Stage > T2 showed a trend toward higher risk of LN involvement (p=0.06 by chi square). There was no correlation between differentiation and stage, and no significant correlation for ERCC1 or TS with grade or stage. Conclusions: EGFR overexpression is common in PSC and correlates with tumor grade but not stage, suggesting it may be important for disease progression. The absence of KRAS mutations may portend responsiveness to EGFR- targeted therapy based on experience in other tumors. Low ERCC1 as an association with platinum response will be explored in an expanded cohort. No significant financial relationships to disclose.