title: Phosphorylation status of epidermal growth factor receptor is closely associated with responsiveness to gefitinib in pulmonary adenocarcinoma.
abstract: 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.
authors.affiliation: Department of Molecular Pathology, Oita University Faculty of Medicine, Oita 879-5593, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Hijiya
authors.forename: Michiyo
authors.initials: M
authors.lastname: Miyawaki
authors.forename: Katsunobu
authors.initials: K
authors.lastname: Kawahara
authors.forename: Shinji
authors.initials: S
authors.lastname: Akamine
authors.forename: Koh-Ichi
authors.initials: K
authors.lastname: Tsuji
authors.forename: Jun-Ichi
authors.initials: J
authors.lastname: Kadota
authors.forename: Shin'ichiro
authors.initials: S
authors.lastname: Akizuki
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Uchida
authors.forename: Keiko
authors.initials: K
authors.lastname: Matsuura
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Tsukamoto
authors.forename: Masatsugu
authors.initials: M
authors.lastname: Moriyama
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D004252:DNA Mutational Analysis; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D000077156:Gefitinib; D015870:Gene Expression; D018773:Genes, erbB-1 / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010766:Phosphorylation; D016133:Polymerase Chain Reaction; D011799:Quinazolines / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D011799:Quinazolines; D066246:ErbB Receptors; D000077156:Gefitinib