Role of c-MET pathway in the outcome prediction of cetuximab-based therapy in patients with recurrent or metastatic squamous cell carcinoma of the head and neck.

5520 Background: Activation of the c-MET oncogene promotes tumor growth, invasion and metastasis in several tumor types. In addition, c-MET has been reported in consort with EGFR and/or be activated as a compensatory pathway in the presence of EGFR blockade resulting a mechanism of acquired resistance to EGFR inhibitors in lung and colorectal carcinoma. We investigated the impact on cetuximab sensitivity of HGF, c-MET, c-MET activation and c-MET gene status in recurrent or metastatic squamous cell carcinoma of the head and neck (HNSCC) patients. Methods: A single-institution retrospective analysis including 50 HNSCC patients was carried out. For each case, formalin-fixed tumor specimens were assayed for HGF, total and phosphorylated Y1234/35 c-MET (p-c-MET) by immunohistochemistry and c-MET gene by FISH. Overexpression criteria were defined by ROC curves for each protein and amplification was defined by >2 copies in at least two of the three studied tumor areas. Results were analyzed for association with ...