血管内皮生长因子C及其受体3在人恶性黑色素瘤组织内的表达及意义

目的 观察人恶性黑色素瘤组织内血管内皮生长因子C(VEGF-C)及其受体3(VEGFR-3)的表达,探讨VEGF-C和VEGFR-3在恶性黑色素瘤淋巴管生成及淋巴道转移中的作用.方法 取人恶性黑色素瘤组织48例(石蜡标本30例,术后新鲜组织18例),应用免疫组织化学和RT-PCR技术,观察VEGF-C和VEGFR-3蛋白及mRNA在恶性黑色素瘤组织内的表达情况.以淋巴管内皮透明质酸受体(LYVE-1)标记淋巴管,计数恶性黑色素瘤组织淋巴管数密度.结果 VEGF-C和VEGFR-3蛋白主要表达于恶性黑色素瘤细胞胞浆内,在肿瘤周围的血管和淋巴管内皮上也可见VEGFR-3蛋白表达,VEGF-C和VEGFR-3蛋白在淋巴结转移组恶性黑色素瘤组织内的表达水平明显高于无淋巴结转移组(P<0.05).在18例新鲜恶性黑色素瘤中,淋巴结转移组VEGF-C和VEGFR-3mRNA的表达明显高于无淋巴结转移组(P<0.01).LYVE-1表达于肿瘤间质内的淋巴管内皮细胞,淋巴结转移组恶性黑色素瘤组织中的淋巴管数密度(LMVD)为9.845±2.454,无淋巴结转移组恶性黑色素瘤组织中的淋巴管数密度为6.534±2.193,淋巴结转移组恶性黑色素瘤组织内的淋巴管数密度明显高于无淋巴结转移组(P<0.01).结论恶性黑色素瘤组织内VEGF-C表达明显增高,并通过上调其受体VEGFR-3的表达促进恶性黑色素瘤组织内淋巴管的生成,从而促进恶性黑色素瘤的淋巴道转移.

Expression and significance of vascular endothelial growth factor C and its receptor 3 in malignant melanoma

Objective To elucidate the effects of vascular endothelial growth factor C (VEGF-C) and vascular endothelial growth factor receptor 3 (VEGFR-3), in malignant melanoma lymphangiogenesis and lymphatic metastasis, we observed the expression of VEGF-C and VEGFR-3 in proteins and mRNA level in malignant melanoma. Methods The expression of VEGF-C and VEGFR-3 protein was examined in 48 human malignant melanoma cases (30 paraffin-embedded specimens and 18 fresh tumor specimens) by immunohistochemistry and VEGF-C and VEGFR-3 mRNA was examined in 18 fresh tumor specimens using RT-PCR. lymphatic vessel endothelial hyaluronic acid receptor(LYVE-1) was measured for detecting lymphatic vessels, and lymphatic vessel density (LMVD) was observed in lymph node metastatic and non-metastatic malignant melanoma. Results VEGF-C and VEGFR-3 proteins were detected in malignant melanoma cells, vascular endothelium and lymphatic endothelium in peritumor stroma also showed VEGFR-3 expression. The expression of VEGF-C and VEGFR-3 protein in lymph node metastatic malignant melanoma was significantly higher than that in the non-metastatic group respectively (P<0.05). Eighteen fresh tissue samples were examined for gene expression of VEGF-C and VEGFR-3 using RT-PCR, the VEGF-C and VEGFR-3 mRNA levels were significantly higher in the lymph node metastatic group than that in the non metastatic group, respectively (P<0.01). LYVE-1 was mainly expressed mainly in the lymphatic endothelium in peritumor stroma, LMVD was 9.845±2.454 and 6.534±2.193 in the metastatic and non-metastatic group, respectively, and the LMVD was significantly higher in the lymph node metastatic group than that in the non-metastatic group (P<0.01). Conclusion Higher expression of VEGF-C in malignant melanoma can up-regulate the expression of VEGFR-3, and the interaction of VEGF-C and VEGFR-3 can facilitate tumor lymphangiogenesis and lymph node metastasis in malignan