Assessment of EGFR and HER2 expression in penile cancer as potential therapeutic targets.

Penile cancer (PC) is a rare but aggressive malignancy with limited systemic treatment options, particularly in advanced stages. Targeted therapies against receptor tyrosine kinases such as EGFR and HER2 have demonstrated clinical benefit in other cancer types, yet their role in PC remains poorly defined. Understanding their expression patterns in primary tumors and metastases is essential for identifying new therapeutic avenues. In this study, we aimed to systematically assess the expression of EGFR and HER2 in a large multicenter PSCC cohort and evaluate their potential relevance not only as therapeutic targets but also as prognostic biomarkers. In addition, we analyzed possible correlations with key clinicopathological features, including HPV status, tumor stage and histological subtype. Among 208 patients, moderate to strong EGFR expression was detected in 27.0% of primary tumors and 29.0% of metastases, with HER2 overexpression observed in 7.0% and 21.4%, respectively. EGFR expression was significantly higher in HPV-negative tumors and associated with reduced overall survival. In contrast, HER2 was more frequently overexpressed in HPV-positive and basaloid tumors without prognostic significance. Expression patterns of both markers were largely homogeneous within primary tumors but showed partial discordance between primary and metastatic lesions. EGFR and HER2 are variably expressed in PC, with EGFR displaying potential as a prognostic marker. These findings suggest that both receptors may serve as therapeutic targets in certain patients, particularly if confirmed in metastases. Future research should integrate molecular profiling to refine biomarker-based stratification and guide the use of targeted therapies in this rare but challenging cancer.