Phosphorylation status of epidermal growth factor receptor is closely associated with responsiveness to gefitinib in pulmonary adenocarcinoma

Twenty-one cases of primary lung carcinoma were analyzed for correlations between the presence of somatic mutations of the epidermal growth factor receptor (EGFR) gene and the phosphorylation status of EGFR, which was analyzed by immunohistochemistry with antibodies recognizing the phosphorylated form of EGFR. Somatic mutations were detected in 11 (52.4%) of the 21 cases. Immunohistochemistry with an antibody recognizing EGFR phosphorylated at tyrosine (pEGFR-tyr) 992 and an antibody recognizing EGFR phosphorylated at tyrosine 1173 (pEGFR-tyr1173) revealed that 12 (57.1%) and 21 (100%) of the 21 cases were positive, respectively. Interestingly, the mutation status of the EGFR gene was strongly correlated with immunoreactivity for pEGFR-tyr992 (P = .0019). pEGFR-tyr992 immunoreactivity was significantly correlated with clinical responsiveness to gefitinib (P = .0011). These findings suggest that immunohistochemical evaluation with anti-pEGFR-tyr992 antibody is useful for prediction of responsiveness to gefitinib.