The molecular status of the
epidermal growth factor receptor (EGFR) has not been as well studied in
head and neck squamous cell carcinoma (
HNSCC) as in
lung cancer. We examined the frequencies of EGFR mutations as well as the expression/phosphorylation status of the EGFR
protein in
HNSCC patients. Moreover, we tried to elucidate associations between EGFR molecular status and patient characteristics and disease-free survival. In this prospective cohort study, clinical data and samples were obtained from 82 consecutive patients who had not been treated with EGFR molecular targeting
therapy. Full-length EGFR was sequenced, and expression and phosphorylation of the EGFR
protein were measured by Western blotting. Four novel mutations (E709K, V765G, Ins770G, and G1022S) and one mutation well-known in
lung cancer (L858R) were identified in six
HNSCC samples (7%), but we could not find any mutations in the extracellular domain of EGFR, such as
EGFRvIII, in this study. E709K and Ins770G as well as L858R appear to be functional mutations based on the use of Ba/F3 cells. In terms of patient characteristics, the number of metastatic lymph nodes and node stage were associated with phosphorylation of EGFR. No patients with EGFR mutations relapsed during the study period. Excluding mutated cases, patients whose
tumor samples showed phosphorylated EGFR relapsed significantly earlier than those without phosphorylated EGFR. This finding was still significant after adjusting for mutation and overexpression of EGFR
protein using the Cox proportional hazard model. In conclusion, phosphorylated EGFR without mutations may be a marker of poor prognosis in patients with
HNSCC.