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Cyclooxygenase-2 Is an Independent Prognostic Factor in Gastric Carcinoma Patients Receiving Adjuvant Chemotherapy and Is Not Associated with EBV Infection

Authors' Affiliations: ¹ Department of Pathology, ² Division of Hematology-Oncology, Department of Medicine, and ³ Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine; ⁴ Biostatistics Unit, Samsung Biomedical Research Institute, Seoul, Korea

Requests for reprints: Kyoung-Mee Kim, Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50, Ilwon-dong, Gangnam-Gu, Seoul 135-710, Korea. Phone: 82-2-3410-2800; Fax: 82-2-3410-6396; E-mail: kkmkys{at}skku.edu.

Purpose: Cyclooxygenase-2 (COX-2) is believed to be involved in carcinogenesis in patients with chronic gastritis with Helicobacter pylori infection. EBV is detected in 10% of gastric carcinomas and H. pylori induces EBV reactivation in the gastric epithelium. We aimed to evaluate significance of COX-2 in gastric carcinoma occurred in EBV and H. pylori prevalent area.

Experimental Design: Tissue microarray samples from 457 gastric carcinoma patients who underwent gastrectomy and adjuvant chemotherapy were studied with EBER1 in situ hybridization for EBV and immunohistochemistry for COX-2 and other gastric carcinoma-related proteins (hMLH1, E-cadherin, c-erbB, and cyclin D1).

Results: EBV infection was observed in 10.9% of gastric carcinomas and was associated with proximal tumor location, increased numbers of lymph node, and E-cadherin expression (P < 0.01). COX-2 overexpression was closely associated with intestinal histologic type and lower tumor stage (P = 0.01). Univariate analysis showed that pT, pN, lymph node ratio, American Joint Committee on Cancer stage, numbers of negative lymph nodes, and resection margin <1 cm were significant prognostic factors. The Cox proportional hazards regression analysis indicated that lack of COX-2 expression and resection margin <1 cm were independent prognostic factors for disease-free survival (P = 0.008 and 0.03, respectively) and overall survival (P = 0.01 and 0.007, respectively).

Conclusions: EBV infection is not associated with COX-2 expression or survival in gastric carcinoma. Lack of COX-2 expression is an independent prognostic factor in both overall and disease-free survival in gastric carcinoma. Our results indicate that COX-2 may play a role in the progression of gastric carcinoma regardless of EBV infection and is closely associated with histologic differentiation and prognosis.