title: Phosphorylation, but not overexpression, of epidermal growth factor receptor is associated with poor prognosis of non-small cell lung cancer patients.
abstract: Epidermal growth factor receptor (EGFR) is commonly overexpressed in non-small cell lung cancer (NSCLC) and its tyrosine kinase phosphorylation is thought to be an ideal target in the treatment of patients with NSCLC. In the present study, we examined surgically obtained specimens from a series of 36 NSCLC patients for expression of EGFR, phosphorylated EGFR (p-EGFR), and HER2 by immunohistochemistry, and also examined the correlation with clinical characteristics. The positive rate of EGFR, p-EGFR, and HER2 was 97.2%, 44.4%, and 88.6%, respectively, and the overexpression rate was 80.6%, 0.0%, and 27.8%, respectively. EGFR overexpression and phosphorylation were seen at almost the same rate in each histological type of squamous and nonsquamous cell carcinoma (squamous vs. nonsquamous; 78.6% vs. 81.8% for EGFR, 35.7% vs. 50.0% for p-EGFR), while HER2 overexpression was seen less frequently in squamous cell carcinoma than in nonsquamous cell carcinoma (0.0% vs. 45.5%, P = 0.003). Univariate analysis revealed that EGFR overexpression was related to good performance status (P = 0.038) but not related to EGFR phosphorylation. EGFR phosphorylation was correlated to short time to progression (TTP) (P = 0.002) and poor prognosis (P = 0.002), although EGFR overexpression, HER2 overexpression, or EGFR-HER2 coexpression were not correlated to TTP or survival. Bivariate analysis showed EGFR phosphorylation was related to short TTP and poor prognosis both in early and advanced stages. Multivariate analyses confirmed that clinical stage, performance status, and p-EGFR expression were independently associated with increasing risk of short TTP and poor prognosis. These results suggest that phosphorylation, but not overexpression, of EGFR may be an important predictor for clinical outcome of NSCLCs.
authors.affiliation: Department of Internal Medicine and Molecular Therapeutics, University of Tokushima School of Medicine, Tokushima, Japan.
authors.forename: Takanori
authors.initials: T
authors.lastname: Kanematsu
authors.forename: Seiji
authors.initials: S
authors.lastname: Yano
authors.forename: Hisanori
authors.initials: H
authors.lastname: Uehara
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Bando
authors.forename: Saburo
authors.initials: S
authors.lastname: Sone
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016001:Confidence Intervals; D066246:ErbB Receptors / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010766:Phosphorylation; D011379:Prognosis; D016016:Proportional Hazards Models; D015996:Survival Rate; D014407:Tumor Cells, Cultured
chemical_list: D066246:ErbB Receptors