title: Phosphorylated epidermal growth factor receptor and cyclooxygenase-2 expression in localized non-small cell lung cancer.
abstract: OBJECTIVE
  The prognostic significance of epidermal growth factor receptor (EGFR) and cyclooxygenase-2 (COX-2) expression remains unestablished, although EGFR and COX-2 are frequently overexpressed in non-small cell lung cancer (NSCLC). Considering the importance of EGFR activation after ligand binding, however, the expression of phosphorylated EGFR (p-EGFR) may have more significance in predicting tumor aggressiveness in NSCLC than either EGFR or COX-2 expression.
  
  
  METHODS
  We studied the relationships between p-EGFR, EGFR, and COX-2 overexpression and examined their association with prognosis in localized NSCLC. The expression of p-EGFR, EGFR, and COX-2 was studied by immunohistochemistry in 77 surgically-resected stage I/II NSCLC cases. EGFR mutational status was determined by sequencing exons 18-21. Correlation of expression with clinical outcome and other biomarkers, including Ki-67 and microvessel density (MVD), was also examined.
  
  
  RESULTS
  Out of the 77 patients, EGFR overexpression was observed in 37 (48.1%), p-EGFR expression was found in 22 (28.6%), and COX-2 overexpression was seen in 45 (58.4%). Expression of p-EGFR was associated with COX-2 overexpression (P = 0.047), but not EGFR overexpression or high Ki-67 (P = 0.087 and P = 0.092, respectively). COX-2 overexpression was significantly associated with high Ki-67 (P = 0.011). Expression of p-EGFR correlated with lower disease-free survival (P = 0.045), but not overall survival. Neither EGFR nor COX-2 overexpression was associated with prognosis.
  
  
  CONCLUSIONS
  p-EGFR appears to be a better indicator for lower disease-free survival than EGFR overexpression itself in localized NSCLC. Pathways other than EGFR activation may influence COX-2 overexpression.
authors.affiliation: Department of Medicine, Duke University Medical Center and Durham Veterans Affairs Hospital, Durham, NC, USA.
authors.forename: Seok Jin
authors.initials: SJ
authors.lastname: Kim
authors.forename: Zahid N
authors.initials: ZN
authors.lastname: Rabbani
authors.forename: Fan
authors.initials: F
authors.lastname: Dong
authors.forename: Robin T
authors.initials: RT
authors.lastname: Vollmer
authors.forename: Ernst-Gilbert
authors.initials: EG
authors.lastname: Schreiber
authors.forename: Mark W
authors.initials: MW
authors.lastname: Dewhirst
authors.forename: Zeljko
authors.initials: Z
authors.lastname: Vujaskovic
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Kelley
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D051546:Cyclooxygenase 2 / Q000096:biosynthesis*; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000096:biosynthesis; D008175:Lung Neoplasms / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D008297:Male; D055806:Microvessels / Q000473:pathology; D008875:Middle Aged; D009389:Neovascularization, Pathologic; D010766:Phosphorylation
chemical_list: D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D051546:Cyclooxygenase 2; D066246:ErbB Receptors