贲门癌组织环氧化酶-2和血管生成因子的表达及其与血管生成的关系

Expression of cyclooxygenase-2 and vascular endothelial growth factor in carcinoma of the gastric cardia and its correlation with angiogenesis

目的:探讨环氧化酶-2(COX-2)和血管生成因子(VEGF)在贲门癌组织中的表达及其与肿瘤血管生成的关系.方法:免疫组化法检测贲门癌手术切除标本46例和癌旁正常黏膜标本21例中COX-2,VEGF表达.采用抗CD34抗体标记微血管内皮细胞,计算微血管密度(MVD).分析COX-2,VEGF表达与MVD和贲门癌主要临床病理特征的相关性.结果:贲门癌组织COX-2,VEGF阳性表达率、MVD值显著高于癌旁正常黏膜的(80.4% vs 14.3%,x^2=26.22,P<0.01;76.1% vs 19.1%,x^2=19.28,P<0.01:31.95±3.87 vs 16.28±1.55,t=17.76,P<0.01).COX-2,VEGF表达、MVD值与肿瘤临床TNM分期和淋巴结转移密切相关,TNM分期中Ⅲ+Ⅳ期的贲门癌组织中COX-2,VEGF表达率、MVD值显著高于Ⅰ+Ⅱ期的(90.3% vs 60.0%,x^2=5.91,P<0.05;96.8% vs 46.7%,x^2=16.13,P<0.01;33.43±3.34 vs 28.90±3.08,t=4.42,P<0.01).伴有淋巴结转移的贲门癌组织中COX-2,VEGF表达率,MVD值显著高于无淋巴结转移的(94.1% vs 41.7%,x^2=15.51,P<0.01:91.2% vs 50.0%,x^2=9.56,P<0.01;33.53±3.21 vs 27.48±1.03,t=6.38,P<0.01).Spearman等级相关分析表明,COX-2,VEGF表达与MVD呈显著正相关(r= 0.823:r=0.892,P<0.01).结论:COX-2,VEGF异常表达及其诱导的血管生成在贲门癌的侵袭和淋巴结转移中起重要作用.

AIM： To investigate the xygenase （COX）-2 and expression of cycloovascular endothelial growth factor （VEGF） in carcinoma of the gastric cardia, and to evaluate the relationship between COX-2, VEGF expression and angiogenesis, and clinicopathological features of carcinoma of the gastric cardia. METHODS： Forty-six resected tumor specimens were obtained from patients with carcinoma of the gastric cardia, and 21 corresponding paracancerous normal tissues were randomly selected as a control group. Immunohistochemical staining was used for detecting the expression of COX-2 and VEGF. Monoclonal antibody against CD34 was used for visualizing vascular endothelial cells, and microvascular density （MVD） was determined by counting the number of CD34-positive vascular endothelial cells. The correlation between COX-2, VEGF expression and MVD and clinicopathological features of the patients was analyzed. RESULTS： The positive expression rate for COX-2, VEGF and MVD in the cancerous tissue was 80.4%, 76.1% and 31.95 ± 3.87 respectively, which was significantly higher than that in the controls （14.3%, 19.1% and 16.28 ± 1.55, respectively; P 〈 0.01）. The mean positive expression rate for COX-2, VEGF and MVD was associated with clinical TNM classification （90.3% vs 60.0%, x^2 = 5.91, P 〈 0.05; 96.8% vs 46.7%, x^2 = 16.13, P 〈 0.01; 33.43 ± 3.34 vs 28.90 ± 3.08, t = 4.42, P 〈 0.01） and lymph node metastasis （94. 1% vs 41.7%, x^2 = 15.51, P 〈 0.01; 91.2% vs 50.0%, x^2= 9.56, P 〈 0.01; 33.53 ± 3.21 vs 27.48 ± 1.03, t = 6.38, P 〈 0.01）. The Spearman rank correlation test showed that tumor MVD was closely associated with COX-2 （r = 0.823, P 〈 0.01） and VEGF （r = 0.892, P 〈 0.01） expression. CONCLUSION： Overexpression of COX-2 and VEGF is related to tumor invasion and lymph node metastasis in carcinoma of the gastric cardia. COX-2 contributes to development of carcinoma of the gastric cardia by promoting VEGF expression and angiogenesis.