人肝癌组织中iNOS、VEGF的表达及微血管密度的病理意义

背景与目的:诱导型一氧化氮合酶(inducible nitric oxide synthase,iNOS)和血管内皮生长因子(vascular endothelial growth factor,VEGF)被认为是诱导和调节肿瘤血管生成,进而影响肿瘤病理进展和预后的重要相关因子。本研究检测人肝细胞癌(hepatocellular carcinoma,HCC)及相应癌旁组织中iNOS、VEGF的表达,探讨其与血管生成的关系,为临床诊治HCC及判断其预后提供理论依据。方法:应用组织芯片技术,采用原位杂交和免疫组化法分析147例HCC组织及癌旁组织中iNOS、VEGF的表达,并用CD34标记免疫组化法检测微血管密度(microvessel density,MVD)。结果:iNOS、VEGF在癌旁组织中的阳性率分别为33.33%和40.82%,而在癌组织中的阳性率分别为86.39%和78.91%,癌组织与癌旁组织比较差异有显著性(P<0.01)。癌组织的MVD值为56.5±12.8,癌旁组织的MVD值为8.4±3.6,两者差异有显著性(P<0.01)。iNOS的表达与肿瘤大小、乙型肝炎表面抗原(HBsAg)相关(P<0.05),而与转移和肿瘤分化程度无关(P>0.05)。VEGF的表达及MVD值与肿瘤大小、转移相关(P<0.05),而与HBsAg和肿瘤分化程度无关(P>0.05)。在癌组织中MVD与VEGF、iNOS的表达呈正相关,VEGF和iNOS之间亦存在正相关关系(P<0.01)。结论:HCC中iNOS及VEGF的表达与肿瘤血管生成有关。癌组

Expressions of inducible nitric oxide synthase and vascular endothelial growth factor and their relationship with microvessel density in hepatocellular carcinoma

BACKGROUND & OBJECTIVE: Inducible nitric oxide synthase (iNOS), and vascular endothelial growth factor (VEGF) are recognized as key factors required for angiogenesis of tumors. They can influence pathologic development and prognosis of tumors. This study was to investigate the correlation of expressions of iNOS and VEGF to angiogenesis of hepatocellular carcinoma (HCC). METHODS: Tissue microarray of 147 specimens of HCC was prepared, VEGF and microvessel density (MVD) were detected using immunohistochemistry, iNOS mRNA was detected by in situ hybridization. RESULTS: Positive rates of iNOS, and VEGF in HCC tissues were higher than those in adjacent noncancerous tissues (86.39% vs. 33.33%, 78.91% vs. 40.82%). Expression levels of iNOS, and VEGF in HCC tissues were significantly higher than those in adjacent noncancerous tissues (P<0.01). MVD in HCC tissues was significantly higher than that in adjacent noncancerous tissues (56.5+/-12.8 vs. 8.4+/-3.6, P<0.01). Expression of iNOS was related with tumor size, and surface antigen of hepatitis B (HBsAg) (P<0.05), but didn't relate with metastasis, and differentiation of the cancer (P>0.05). Expression of VEGF, and MVD were correlated to tumor size, and metastasis (P<0.05), not to HbsAg, and tumor differentiation (P>0.05). In cancer tissues, MVD was positively correlated with expressions of VEGF and iNOS (P<0.01), expression of VEGF was positively correlated with that of iNOS (P<0.01). CONCLUSION: iNOS and VEGF may play important roles in angiogenesis of HCC. Expression levels of iNOS and VEGF, and MVD in HCC tissues were higher than those in adjacent noncancerous tissues.