Cyclooxygenase-2 promotes angiogenesis by increasing vascular endothelial growth factor and predicts prognosis in gallbladder carcinoma

• Published in: World journal of gastroenterology : WJG Vol. 11; no. 24; pp. 3724 - 3728
• Main Authors: Zhi, Ying-Hui, Liu, Ruo-Shan, Song, Mao-Min, Tian, Yu, Long, Jin, Tu, Wei, Guo, Ren-Xuan
• Format: Journal Article
• Language: English
• Published: United States Department of General Surgery,Affiliated Beijing Tiantan Hospital, Capital University of Medical Sciences, Beijing 100050, China%Department of Anesthesiology, Changhai Hospital of the Second Military Medical University, Shanghai 200433, China%Second Department of General Surgery, First Affiliated Hospital, China Medical University, Shenyang 110001, Liaoning Province, China 28.06.2005; Baishideng Publishing Group Inc
• Subjects: Adult; Clinical Research; Cyclooxygenase 2; Female; Gallbladder Neoplasms - blood supply; Gallbladder Neoplasms - metabolism; Gallbladder Neoplasms - mortality; Humans; Male; Membrane Proteins; Microcirculation; Middle Aged; Neovascularization, Pathologic - metabolism; Neovascularization, Pathologic - mortality; Neovascularization, Pathologic - pathology; Predictive Value of Tests; Prognosis; Prostaglandin-Endoperoxide Synthases - metabolism; Vascular Endothelial Growth Factor A - metabolism; Cyclooxygenase; Gallbladder neoplasms; Neovascularization; Vascular endothelial growth factor
• ISSN: 1007-9327; 2219-2840
• DOI: 10.3748/wjg.v11.i24.3724

To investigate the relationships between the expression of cyclooxygenase-2 (COX-2), vascular endothelial growth factor (VEGF) and the degree of vascularization, clinicopathologic feature, survival time of patients with gallbladder carcinomas. Sixty-four gallbladder carcinoma specimens were evaluated for COX-2, VEGF expression by immunohistochemical methods. Microvessel counts (MVC) were determined using CD(34). The relationships between COX-2, VEGF expression, CD(34)-stained MVC, clinicopathologic features and survival time were analyzed. The correlations between COX-2 and VEGF expression, CD(34)-stained MVC were also investigated. COX-2, VEGF immunoreactivity were observed in 71.9% (46/64) and 54.7% (35/64) specimens, respectively. The average MVC in 64 cases of gallbladder carcinoma was 57+/-14 per high power vision field. The status of MVC was closely correlated with Nevin staging, tumor differentiation and lymph node metastasis (P<0.01, 0.002, and 0.003, 0.000, respectively). Increased VEGF expression was significantly correlated with tumor differentiation (poorly and moderately>well differentiated, P<0.05, P = 0.016). Clinical stages had no relation with the expression of VEGF (P>0.05, P = 0.612). There was a positive correlation between COX-2 expression and clinical stages. The positive rate of COX-2 was higher in cases of Nevin stages S(4)-S(5) (81.8%) than in those of Nevin stages S(1)-S(3) (50.0%) with a statistical significance (P<0.01, P = 0.009). The expression of COX-2 did not vary with differentiation (P>0.05, P = 0.067). Statistically significant differences were also observed according to lymph node metastasis, COX-2 expression and VEGF expression (P<0.01, 0.000, and 0.001, respectively). There was no relation between VEGF, COX-2 expression, MVC and the age and sex of patients. MVC and VEGF positive rate in the COX-2 positive gallbladder carcinoma tissue was higher than that in the COX-2 negative tissue (P<0.05, 0.000, and 0.032, respectively). Patients with VEGF, COX-2 positive tumors had a significantly shorter survival time than those with negative tumors (P<0.05, 0.004, 0.01, respectively). Augmented tumor neovascularization induced by VEGF may be one of the several effects of COX-2 responsible for poor prognosis of human gallbladder carcinoma. COX-2 inhibitor, either in combination therapy with other agents, or for chemoprevention, may be effective via suppression of angiogenesis in this fatal disease.