EGFR Gene Status Correlates with Erk Pathway Activation and Poor Outcome in HPV-Negative Oropharyngeal and Sinonasal Carcinomas

Background: Personalized medicine requires a deep understanding of the molecular profile of tumours. Our aim was to investigate major biomarkers in head and neck carcinomas, including HPV-infection, EGFR gene and the ERK pathway activation. Methods and findings: Carcinomas from the oropharynx (n=55) and sinonasal tract (n=51) were included. HPV was analyzed through p16 immunostain and PCR; EGFR gene expression and copy number, by immunohistochemistry and FISH, respectively. The activation of the ERK pathway was investigated through the expression of ERK1/2. Inverse relationship between HPV-infection and EGFR gene copy number was found (p<0.01). EGFR gene copy number and expression correlated with ERK1/2 expression (p<0.001). Overall survival correlated directly with HPV infection (p=0.004) and inversely with EGFR copy number (p=0.016) and ERK1/2 expression (p=0.015). Conclusions: High-EGFR gene copy number and expression usually involve HPVnegative carcinomas and correlate with ERK1/2 pathway activation and poor outcome. These results may have a high translational relevance.