title: E-cadherin expression and epidermal growth factor receptor mutation status predict outcome in non-small cell lung cancer patients treated with gefitinib.
abstract: It is known that an epidermal growth factor receptor (EGFR) gene mutation(s) is present in a percentage of non-small cell lung cancers (NSCLCs). Gefitinib, an inhibitor of the tyrosine kinase activity of EGFR, is effective on most of them. The EGFR mutation status alone cannot fully predict the response to gefitinib and the prognosis for the patients. We hypothesized that information on the expression levels of phosphorylated-EGFR and -Akt, and E-cadherin, alone or in combination with information on the EGFR mutation, may refine our ability of prediction. We investigated 24 NSCLCs that had recurred after surgery and were treated with gefitinib. Specimens resected by surgery were subjected to the peptide nucleic acid-locked nucleic acid polymerase chain reaction clamp reaction to determine the EGFR mutation status, and to immunohistochemical staining of phosphorylated-EGFR and -Akt, and E-cadherin to determine their expression levels. The EGFR mutation status was predictive of responsive disease (complete response: CR + partial response: PR) and controlled disease (CR + PR + stable disease: SD). Positive E-cadherin staining was predictive of longer time to progression (12.4 vs. 5.9 months, p<0.05) and overall survival (OS) (18.4 vs. 13.0 months, p<0.05). Together the patients with an EGFR mutation and the patients with positive E-cadherin staining defined a patient group with a median OS of 18.4 months and excluded the patient group with the median OS of 3.7 months. Neither p-Akt nor p-EGFR staining was associated with the response and survival. In patients with surgically resected NSCLC tumors, the EGFR mutation status and E-cadherin staining can select patients who will benefit from gefitinib therapy.
authors.affiliation: Department of Pulmonary Medicine/Infection and Oncology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo, Japan.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Miyanaga
authors.forename: Akihiko
authors.initials: A
authors.lastname: Gemma
authors.forename: Masahiro
authors.initials: M
authors.lastname: Ando
authors.forename: Seiji
authors.initials: S
authors.lastname: Kosaihira
authors.forename: Rintaro
authors.initials: R
authors.lastname: Noro
authors.forename: Yuji
authors.initials: Y
authors.lastname: Minegishi
authors.forename: Kiyoko
authors.initials: K
authors.lastname: Kataoka
authors.forename: Michiya
authors.initials: M
authors.lastname: Nara
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Okano
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Miyazawa
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Tanaka
authors.forename: Akinobu
authors.initials: A
authors.lastname: Yoshimura
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Kobayashi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Iwanami
authors.forename: Koichi
authors.initials: K
authors.lastname: Hagiwara
authors.forename: Eitaka
authors.initials: E
authors.lastname: Tsuboi
authors.forename: Shoji
authors.initials: S
authors.lastname: Kudoh
mesh_terms: D015820:Cadherins / Q000032:analysis / Q000378:metabolism*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D004252:DNA Mutational Analysis; D019008:Drug Resistance, Neoplasm; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics*; D005260:Female; D000077156:Gefitinib; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010766:Phosphorylation; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D051057:Proto-Oncogene Proteins c-akt / Q000032:analysis / Q000378:metabolism; D011799:Quinazolines / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D015820:Cadherins; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D066246:ErbB Receptors; D051057:Proto-Oncogene Proteins c-akt; D000077156:Gefitinib