血管内皮生长因子C及其受体3在胃癌组织中的表达及意义

Expression of Vascular Endothelial Growth Factor(VEGF) C and VEGF Receptor 3 in Gastric Carcinoma

目的探讨血管内皮生长因子C(VEGF-C)和受体(VEGFR)-3在人胃癌组织中的表达及其与微血管、微淋巴管形成、淋巴转移、预后之间的关系。方法对56例人胃癌及相应癌旁组织行VEGF-C,VEGFR-3及CD34免疫组织化学染色链霉素抗生物素蛋白-过氧化物酶(SP)法检测,进行淋巴管密度计数、微血管密度(MVD)计数。结果①VEGF-C在胃癌细胞中的表达:VEGF-C阳性表达主要位于胃癌细胞胞浆和胞膜,胃癌组织中VEGF-C的阳性表达率明显高于对照组(P<0.01)。②VEGFR-3表达:VEG-FR-3表达定位于胃癌细胞和脉管内皮细胞的胞膜或胞浆。③VEGF-C与VEGFR-3间相关性:VEGF-C阳性表达的胃癌细胞VEGFR-3也多呈阳性表达,二者有相关性(r=0.439,P<0.05)。④胃癌中VEGF-C的表达与胃癌分化程度呈负相关(P<0.05);VEGF-C表达与胃癌浸润深度和局部淋巴结转移相关。侵及肌层和肌层以上胃癌组织VEGF-C表达阳性率明显高于未侵及肌层者(P<0.05);有淋巴结转移的26例患者中VEGF-C表达阳性率高于无淋巴结转移组(P<0.05);胃癌细胞中VEGFR-3的表达与肿瘤大小、浸润深度和局部淋巴结转移相关;淋巴管数与肿瘤大小、浸润深度和局部淋巴结转移相关。⑤经Kaplan-Meier生存分析,VEGF-C是影响患者术后生存的独立性指标。结论胃癌中,VEGF-C通过自分泌方式作用于受体VEGFR-3,促进胃癌组织生长,抑制分化。VEGF-C促使胃癌内淋巴管形成,促进胃癌淋巴结转移。VEGF-C和VEGFR-3表达增高、淋巴管密度增加是促使胃癌发生淋巴结转移的重要原因。VEGF-C促进微血管的形成。VEGF-C表达有推测预后的意义。

Objective To study the relationship between angiogenesis and lymphangiogenesis with the expression of vascular endothelial growth factor C(VEGFC) and VEGFR-3 in human gastric carcinoma.Methods Samples of 56 gastric carcinoma cases with the neighboring noncancerous tissue were studied using anti-VEGFC,VEGFR-3 and CD34 antibodies.Assessment of lymphatic vessel density and microvessel density(MVD) were performed.Results ①The expression of VEGF-C in gastric carcinoma was significantly higher than that in control(73.2% vs 20.0% P<0.01) Immunohistological staining with VEGF-C specific polyclonal antibody showed cytoplasmic and membranous staining in the cancer cells.②The positive expression of VEGFR-3 is chiefly located in cytomembrane and cytoplasm of cancer cells and vessel endothelial cel1s.③By spearman correlation analysis,We found that in cancer cells,VEGF-C expression correlated withVEGFR-3 expression(r=0.439,P<0.05).④VEGF-C expression in gastric carcinoma were negatively associated with the differentiation of tumor cell(P<0.05);The Positive expression of VEGF-C in cases that penetrate into muscle and serosa is significantly higher than that into mucosa and submucosa group(80.4% vs 40%,P<0.05);the positive expression of VEGF-C in 1ymPh node metastasis group is higher than that in no 1ymph node metastasis group(82.9% vs 12.0%,P<0.05);The expression of VEGFR-3 in cancer cell is associated with tumor size,infiltration depth and 1ymph node metastasis.Lymphatic vessel density is associated with tumor size,infiltration depth 1ymph node metastasis.⑤By Kaplan-Meier survival analysisan VEGF-C expression is found to be in dependent factors for Patients prognosis.Conclusion VEGF-C in gastric carcinoma.are related to lymphangiogenesis and angiogenesis,as well as to the occurrence and the development of gastric carcinoma.VEGF-C promotes intratumoral lymphangiogenesis via VEGFR-3,resulting facilitated invasion of cancer cells into the lymphatic vessels VEGF-C expression can be a useful predictor of poor prognosis in gastric carcimona.