title: Prognostic significance of epidermal growth factor receptor phosphorylation and mutation in head and neck squamous cell carcinoma.
abstract: 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.
authors.affiliation: Division of Molecular Epidemiology, Jikei University School of Medicine, Minato-ku, Tokyo, Japan.
authors.forename: Takanori
authors.initials: T
authors.lastname: Hama
authors.forename: Yuki
authors.initials: Y
authors.lastname: Yuza
authors.forename: Yoshimichi
authors.initials: Y
authors.lastname: Saito
authors.forename: Jin
authors.initials: J
authors.lastname: O-uchi
authors.forename: Shu
authors.initials: S
authors.lastname: Kondo
authors.forename: Masataka
authors.initials: M
authors.lastname: Okabe
authors.forename: Hisashi
authors.initials: H
authors.lastname: Yamada
authors.forename: Takakuni
authors.initials: T
authors.lastname: Kato
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Moriyama
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kurihara
authors.forename: Mitsuyoshi
authors.initials: M
authors.lastname: Urashima
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism; D005260:Female; D018628:Gene Dosage; D015972:Gene Expression Regulation, Neoplastic; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D006801:Humans; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D010766:Phosphorylation; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D017422:Sequence Analysis, DNA
chemical_list: D014408:Biomarkers, Tumor; D066246:ErbB Receptors