Tumor COX-2 expression and prognosis of patients with resectable pancreatic cancer

Abstract

Background: COX-2 is over-expressed in many cancers and precursor neoplasms including pancreatic cancer and in experimental settings its overexpression has multiple tumorigenic effects including increasing proliferation and angiogenesis, and inhibition of apoptotic and immunologic responses. We evaluated the prognostic significance of COX-2 expression in pancreatic adenocarcinomas. Patients and Methods: We analyzed COX-2 expression by immunohistochemistry in a prospective cohort of 299 patients with resectable infiltrating adenocarcinoma of the pancreas that had undergone a pancreaticoduodenectomy at Johns Hopkins Hospital between January of 1998 and July of 2003. The survival associated with COX-2 expression was assessed by Kaplan-Meier survival analysis and multivariate Cox proportional hazards regression models that controlled for other known prognostic factors associated with pancreas cancer mortality. Results: By Kaplan-Meier analysis, patients whose pancreatic cancer cells expressed COX-2 (median survival, 15 months) had a significantly worse prognosis than patients whose tumor cells did not express COX-2 (median survival, 20 months; log rank, P=0.002). In the multivariate Cox regression model (which included tumor size, node status, margin status, histologic grade, and age), COX-2 expression remained independently prognostic of a worse survival with a hazard ratio (HR) of 1.41 (95% CI 1.08-1.84, P=0.01). However, the adverse prognosis associated with COX-2 expression appeared greater in larger tumors: For tumors ≥ 3cm in diameter, the HR was HR of 1.52 (95% CI 1.04-2.22) versus 1.11 (95% CI 0.75-1.67) in cancers < 3cm. Conclusions: Tumor COX-2 expression portends a poor prognosis for patients with resected adenocarcinoma of the pancreas, particularly in tumors ≥ 3 cm.