胰腺癌组织中淋巴管生成的机制及意义

Expressions of VEGF-C, D/VEGFR-3 in pancreatic cancer and their clinical significance

目的:探讨胰腺癌组织中血管内皮生长因子C(vascular endothelial growth factor-C,VEGF-C)、血管内皮生长因子D(vascular endothelial growth factor-D,VEGF-D)与微淋巴管密度(microvessel vessd density,MLVD)、微血管密度(microvessel density,MVD)及淋巴结转移之间的相关关系,阐明癌周淋巴管增生的机制及意义。方法:免疫组化检测30例胰腺癌组织中VEGF-C、VEGF-D、血管内皮生长因子受体3(vascular endothelialg rowth factor receptor-3,VEGFR-3)(MLVD)以及CD34(MVD)蛋白的表达,RT-PCR检测VEGF-A、VEGF-C、VEGF-DmRNA在30例胰腺癌新鲜组织中的表达。结果:VEGF-C、VEGF-D蛋白阳性率分别为73%(22/30)和57%(17/30),肿瘤周边部位显著高于肿瘤中心部位,差异有统计学意义,P<0·05;其表达与肿瘤的部位、分化程度以及组织学类型无关,而与肿瘤的TNM分期有关,Ⅲ、Ⅳ期显著高于Ⅰ、Ⅱ期。在VEGF-C蛋白阳性组,MVD高于阴性组,P=0·0472,MLVD亦高于阴性组,P<0·01,淋巴结转移增多,P=0·0318;VEGF-D蛋白阳性组与阴性组相比MVD无变化,P=0·07,MLVD高于阴性组,P<0·01,淋巴结转移增加,P=0·0179。结论:VEGF-C参与胰腺癌血管生成和淋巴管生成的调控,VEGF-D只参与淋巴管生成的调控。VEGF-C和VEGF-D诱导胰腺癌淋巴管生成,促进肿瘤细胞淋巴道转移。

OBJECTIVE： To investigate the relationship between VEGF-C, VEGF-D, MLVD, MVD and lymph node metastasis in pancreatic cancer, and elucidate the mechanism and significance of the cancerous peripheral tissue lymphatic. METHODS： The expressions of VEGF-C, VEGF-D, MLVD,MVD were assayed by means of immunohistochemistry in 30 patients with pancreatic carcinoma. RESULTS： The positive rates of VEGF-C, VEGF-D were 73% （22/30）, 57% （17/30） respectively in pancreatic cancer. The expressions of VEGF-C and VEGF-D in cancerous invasive edge were significantely higher than those in the center of cancerous tissues （P〈0.05）. There was no correlation between the expressions of VEGF-C, VEGF-D and the site, differentiation, histology types. Ⅲ, Ⅳ stages of pancreatic cancer showed strong expressions of VEGF-C,VEGF-D than Ⅰ , Ⅱ stages of pancreatic （P〈0.01）. The MVD, MLVD and positive lymph node in positive VEGF-C group were higher than in the negative group. The MLVD and positive lymph node in positive VEGF-D group were higher than those in the negative group. CONCLUSIONS： VEGF-C participates in the regulation of angiogenisis and lymphangiogenisis in pancreatic cancer, but VEGF-D only participates in the regulation of lymphangiogenisis. VEGF-C and VEGF-D induce lymphangiogenisis in pancreatic cancer and promote the tumor cell lymph metastasis.