Prognostic significance of cyclooxygenase 2 expression in 259 cases of non-small cell lung cancer

Context.-Previous studies report that increased expression of cyclooxygenase 2 (COX-2) correlates with poor clinical outcome in several malignancies, including non-small cell lung carcinoma (NSCLC). Cyclooxygenase 2 inhibitors have been reported to effectively inhibit carcinogenesis in colon cancer experimental models. Objective.-We examined COX-2 expression in 259 cases of NSCLC to evaluate its prognostic significance. Design.-Sections of NSCLC from patients with a median 5-year follow-up were immunostained with COX-2 monoclonal antibody (1:150) using the Dako mouse EnVision+ system. Extent of COX-2 expression in neoplastic cells was recorded as follows: 0, 0% to 10% of cells positive; 1, 11% to 33% positive; 2, 34% to 66% positive; and 3, more than 66% positive. Intensity was scored as either increased (+) or not increased (-), compared to internal control smooth muscle and endothelial cells. Kaplan-Meier analysis was used to assess the relationship between survival and COX-2 expression, using the log-rank test for statistical significance. Results.-No relationship was found between the extent and/or the intensity of COX-2 expression and patient survival when the entire cohort was considered. However, when separately analyzed according to disease stage and intensity of COX-2 expression, a significant relationship (P = .03) between increased COX-2 expression and shortened patient survival was found only in patients with stage I and II NSCLC. Conclusions.-To our knowledge, this is the largest series of NSCLCs in which COX-2 has been investigated as a prognostic marker. The findings in this large series support previous studies of smaller cohorts that reported that increased COX-2 expression predicts poor outcome in patients with early-stage NSCLC.