Ding Ming Xing, Li Ji Cheng, Tang Xin Hua
Department of Lymphology, Institute of Cell Biology, Zhejiang University, Hangzhou 310031, China.
Shi Yan Sheng Wu Xue Bao. 2003 Dec;36(6):445-52.
The aim of the present study was to explore the role of vascular endothelial growth factor-C (VEGF-C) in the process of angiogenesis, lymphangiogenesis and lymphatic metastasis in epithelial ovarian tumors. In situ hybridization and immunohistochemical staining for VEGF-C were performed in 30 epithelial ovarian carcinomas, 9 borderline tumors and 26 benign cystadenomas. Endothelial cells were immunostained with anti-VEGFR-3 pAb and anti-CD31 mAb, and VEGFR-3 positive vessels and microvessel density (MVD) were assessed by image analysis. VEGF-C mRNA and protein expression in ovarian epithelial carcinomas were significantly higher than that in borderline tumors and benign cystadenomas (p < 0.05 or p < 0.01). In ovarian epithelial carcinomas, VEGF-C protein expression, VEGFR-3 positive vessels and MVD were significantly higher in the cases of clinical stage III-IV and with lymphatic metastasis than those of clinical stage I-II and without lymphatic metastasis respectively (p < 0.05 or p < 0.01), VEGFR-3 positive vessels and MVD was significantly higher in the VEGF-C protein positive tumors than negative tumors (p < 0.05), VEGFR-3 positive vessels was significantly correlated with MVD(p < 0.01). These data suggest that VEGF-C might play a role in lymphatic metastasis via lymphangiogenesis and angiogenesis in epithelial ovarian carcinomas, and VEGF-C could be used as a biologic marker of metastasis in ovarian epithelial carcinomas.
本研究的目的是探讨血管内皮生长因子-C(VEGF-C)在上皮性卵巢肿瘤血管生成、淋巴管生成及淋巴转移过程中的作用。对30例上皮性卵巢癌、9例交界性肿瘤及26例良性囊腺瘤进行VEGF-C的原位杂交及免疫组化染色。用抗VEGFR-3 pAb和抗CD31 mAb对内皮细胞进行免疫染色,通过图像分析评估VEGFR-3阳性血管及微血管密度(MVD)。卵巢上皮癌中VEGF-C mRNA和蛋白表达显著高于交界性肿瘤和良性囊腺瘤(p<0.05或p<0.01)。在卵巢上皮癌中,临床分期为III-IV期且有淋巴转移的病例,其VEGF-C蛋白表达、VEGFR-3阳性血管及MVD分别显著高于临床分期为I-II期且无淋巴转移的病例(p<0.05或p<0.01),VEGF-C蛋白阳性肿瘤的VEGFR-3阳性血管及MVD显著高于阴性肿瘤(p<0.05),VEGFR-3阳性血管与MVD显著相关(p<0.01)。这些数据表明,VEGF-C可能通过淋巴管生成和血管生成在上皮性卵巢癌的淋巴转移中发挥作用,且VEGF-C可作为卵巢上皮癌转移的生物学标志物。