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

Paola Castillo, Alba Diaz, Sofia Hakim, Ana B. Larque, Aron Sousa, Carla uster, Nuria Guimera, Wim Quint, Alfons Nadal, Juan J. Grau, Jaume Ordi and lucia Alos

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.