Immunohistochemical and genetic evaluations of epidermal growth factor receptor (EGFR) in oral squamous cell carcinoma

Objectives: To study the role of epidermal growth factor receptor (EGFR) in oral squamous cell carcinoma (OSCC), protein expression, gene amplification, and mutations were analyzed in OSCC as well as leukoplakia. Immunoreactivity of Ki-67 and K-Ras gene mutations were simultaneously evaluated. Material and methods: Eighty-two OSCC and 10 leukoplakia specimens were immunohistochemically examined with antibodies against EGFR and Ki-67. Amplification of EGFR was evaluated by chromogenic in situ hybridization (CISH). In 14 OSCC samples, EGFR exons 19, 21 and K-Ras exon 2 were analyzed by direct DNA sequencing. Results: Immunohistochemical reactivity for EGFR and Ki-67 was detected in epithelial cells of leukoplakia and in carcinoma cells of OSCC. EGFR and Ki-67 immunoreactivity was significantly higher in OSCC than in leukoplakia. Leukoplakia showed no EGFR amplification, whereas OSCC exhibited low-level amplification in 19 cases and high-level amplification in 3 cases, respectively. OSCC cases with EGFR amplification showed slightly higher EGFR and Ki-67 immunoreactivity than those without amplification. In OSCC, EGFR immunoreactivity significantly correlated with the mode of invasion, invasion depth, as well as EGFR amplification significantly correlated with the degree of differentiation, mode of invasion, recurrence, and postoperative metastasis. Direct DNA sequencing of EGFR and K-Ras did not show any gene alterations in OSCC. Conclusion: EGFR aberrations might contribute to carcinogenesis, invasion, metastasis as well as poor outcomes in OSCC. EGFR-targeting therapy with anti-EGFR monoclonal antibody agents may be beneficial in OSCC patients.