Combined analysis of cyclooxygenase-2 expression with p53 and Ki-67 in nonsmall cell lung cancer

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 (<= 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.