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Prognostic Significance of VEGF Expression in Correlation With COX-2, Microvessel Density, and Clinicopathological Characteristics in Human Gastric Carcinoma

¹ Surgical Oncology, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku 113-8519 Tokyo, Japan
² Translational Oncology, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku 113-8519, Tokyo, Japan
³ Vascular and Applied Surgery, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku 113-8519, Tokyo, Japan

Correspondence: Address correspondence and reprint requests to: Yanislav Kolev, MD; E-mail: kolev.srg2{at}tmd.ac.jp

Background: Many studies have shown that angiogenesis plays an important role in the process of cancer development and progression. Vascular endothelial growth factor (VEGF) has a potent angiogenic activity, and cyclooxygenase-2 (COX-2) supports angiogenesis by regulated production of angiogenic factors, including VEGF. The purpose of this study was to examine the expression of VEGF in combination with COX-2 and CD34, their correlation with various clinicopathological factors, and their prognostic significance in human gastric carcinoma.

Methods: Specimens from 169 patients with different grade and stage gastric carcinoma were investigated by immunohistochemistry for COX-2 and VEGF expression. Tumor microvessel density was assessed with CD34 immunostaining. Correlations between the expression of VEGF, COX-2, CD34, and various clinicopathological factors were studied. The effect of these proteins on patient survival was determined.

Results: COX-2 and VEGF were positively expressed in 36.7% and 50.3% of the patients, respectively. Positive correlation was found between VEGF and COX-2 and between VEGF and CD34. VEGF expression was correlated with depth of invasion; metastatic lymph nodes; lymphatic and venous invasion; and tumor, node, metastasis system stage. Patients with positive staining for VEGF showed far lower disease-free (64.9% vs. 81.3%) and overall (58.3% vs. 76.9%) survival rates than VEGF-negative patients. In multivariate analysis, only tumor location, depth of invasion, and lymph node metastasis were shown to be independent prognostic factors.

Conclusions: VEGF expression correlates with angiogenesis and tumor progression and is a valuable prognostic factor in patients with gastric carcinoma.

Key Words: VEGF • COX-2 • Angiogenesis • Prognosis • Gastric cancer

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