title: Combined analysis of cyclooxygenase-2 expression with p53 and Ki-67 in nonsmall cell lung cancer.
abstract: BACKGROUND
  Cyclooxygenase-2 (COX-2) is known to play a role in carcinogenesis and tumor progression. The aim of this study was to evaluate the relationship between COX-2 expression and clinicopathologic features, and to define the importance of COX-2 expression alone and in combination with p53 and Ki-67 expression in the clinical outcome of NSCLC.
  
  
  METHODS
  A total of 219 patients with stage I-IIIB nonsmall cell lung cancer (NSCLC) who previously underwent surgery were analyzed in this study. The COX-2 expression was evaluated by means of immunohistochemistry; p53 and Ki-67 immunoreactivity were also studied.
  
  
  RESULTS
  The COX-2 expression was observed in 137 patients (63%) and was significantly associated with lymph node metastasis and the histological grade of those with adenocarcinoma (p = 0.02 and 0.04, respectively). Kaplan-Meier analyses revealed that COX-2 expression was correlated with poor survival (p = 0.005), whereas multivariate survival analysis did not reveal COX-2 expression to be an independent prognostic factor. When the patients were stratified according to gender, age, tumor histology, and disease stage, COX-2 expression was significantly associated with unfavorable prognosis in males, younger patients (< or = 65 years), and those with adenocarcinoma and stage I tumors. The prognosis of patients with tumors negative for both COX-2 and p53 expression was significantly favorable, whereas those with tumors positive for COX-2 expression and with a high Ki-67 labeling index had a significantly unfavorable prognosis.
  
  
  CONCLUSIONS
  These findings indicate that combined immunohistochemical analysis of COX-2 with p53 and Ki-67 can be useful for identifying the prognosis of NSCLC patients.
authors.affiliation: Department of General Thoracic Surgery, Omiya Medical Center, Jichi Medical School, Omiya, Saitama, Japan. h-tsubochi@omiya.jichi.ac.jp
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Tsubochi
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Sato
authors.forename: Misae
authors.initials: M
authors.lastname: Hiyama
authors.forename: Mitsuomi
authors.initials: M
authors.lastname: Kaimori
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Endo
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Sohara
authors.forename: Tadashi
authors.initials: T
authors.lastname: Imai
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D051546:Cyclooxygenase 2 / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000096:biosynthesis*; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D011013:Pneumonectomy; D011379:Prognosis; D012306:Risk; D016019:Survival Analysis; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis*
chemical_list: D019394:Ki-67 Antigen; D016159:Tumor Suppressor Protein p53; D051546:Cyclooxygenase 2