肝细胞肝癌中COX-2、VEGF表达与肿瘤血管生成及其临床病理意义

SIGNIFICANCE OF CYCLOOXYGENASE-2, VASCULAR ENDOTHELIAL GROWTH FACTOR EXPRESSION AND ANGIOGENESIS IN HEPATOCELLULAR CARCINOMA

目的 研究环氧合酶- 2 (COX- 2 )、血管内皮生长因子(VEGF)蛋白表达水平和肿瘤血管形成在肝细胞肝癌(HCC)组织中的临床病理意义。方法 应用免疫组化方法检测4 4例肝细胞癌患者手术切除石蜡包埋标本的COX- 2、VEGF的蛋白表达,抗CD34单克隆抗体显示血管内皮细胞,根据CD34阳性的血管内皮细胞计数来测定肿瘤微血管密度(MVD)。结果 高分化HCC中COX- 2蛋白表达显著高于中分化和低分化HCC(P<0 .0 5 ) ;转移组COX- 2蛋白表达显著高于无转移组(P<0 .0 1)。转移组VEGF蛋白表达显著高于无转移组(P<0 .0 1) ;无包膜HCC中VEGF蛋白表达显著高于有包膜HCC(P<0 . 0 5 )。转移组MVD显著高于无转移组(P<0 .0 1)。COX- 2和VEGF及VEGF和MVD之间表达的强弱呈强正相关(分别r=0 .6 2 6 1,r=0 .6 0 97;均P<0 .0 0 1) ;COX- 2和MVD之间无相关性(r=1.30 4 ,P>0 .0 5 )。结论 COX- 2的过度表达可能与高分化HCC致癌有关;COX- 2及VEGF均与肝癌的转移相关;COX- 2表达与VEGF表达可能有协同效应,共同促进了肿瘤血管的生成,从而促进HCC的生长、浸润和转移。

Objective To investigate the significance of cyclooxygenase-2(COX-2), vascular endothelial growth factor(VEGF) protein expression and angiogenesis in hepatocellular carcinoma(HCC). Method Tissue sections from 44 HCC patients were examined immunohistochemically for protein expression of COX-2 and VEGF. Microvessel density (MVD) was counted by endothelial cells immunostained by anti-CD34 antibody.Results The well differentiated HCC expressed COX-2 protein stronger than moderately differentiated HCC and poor differentiated HCC (P<0.05, respectively). The cases with metastasis in the HCC expressed COX-2 protein stronger than those without metastasis (P<0. 01). The VEGF protein expression of the cases with metastasis in the HCC was greater than those without metastasis (P<0.01). Compared with capsular containment, the VEGF protein expression without capsular containment in the HCC was significantly increased(P<0.05). The MVD of HCC with metastasis was significantly greater than that without metastasis (P<0.01).VEGF expression was positively correlated with COX-2 expression and MVD(r=0.6261, P<0.001;r= 0.6097,P<0.001,respectively). No correlation between COX-2 expression and MVD was observed (r=1.304, P>0.05). Conclusion The result of the present study suggests that COX-2 may be involved in carcinogenesis of well differentiated HCC. COX-2 and VEGF may act on the metastasis of HCC. The co-expression of COX-2 and VEGF might play an important role in angiogenesis, thus promotes the growth, invasion and metastasis of HCC.