大肠癌组织中血管内皮生长因子D表达与预后的关系

The expression of VEGF-D and prognosis of patients with colorectal carcinoma

目的研究血管内皮生长因子D(VEGF-D)在大肠癌中的表达,探讨其表达水平与大肠癌临床病理特征、微血管密度(MVD)及预后的关系。方法抽取1996年1月至1998年1月于瑞金医院外科行结直肠癌根治术且接受正规随访的大肠癌病例69例;所有病例术后第1、2年每3个月、第3年每6个月、第4年后每年1次接受门诊随访,包括体格检查、血清癌胚抗原(CEA)检测、胸片、肝脏B超、腹部CT等。采用免疫组织化学技术检测VEGF—D在69例大肠癌及20例正常大肠组织的表达;采用抗CD34免疫组织化学技术评价大肠癌MVD;采用Axioplan 2 imaging显微图像分析系统对免疫组织化学染色结果进行定量。结果所有(69／69)大肠癌组织和25%(5／20)正常大肠组织检测到VEGF-D表达,染色定位于肿瘤细胞浆。VEGF-D表达显著高于相应正常大肠组织 (P<0．01);VEGF—D表达与大肠癌患者年龄(≤68岁;>68岁)、淋巴结转移及肿瘤浸润深度显著相关(P<0．05);VEGF-D表达与大肠癌患者性别、远处转移、临床分期、分化程度及肿瘤部位相关性均无统计学意义。VEGF—D表达与大肠癌MVD显著相关(P<0．05);VEGF-D高表达的大肠癌患者组总生存期和无瘤生存期显著低于VEGF—D低表达患者组(P<0．05)。结论 VEGF—D在大肠癌中有异常高表达,且与无瘤生存与总生存率显著相关,可用于判断大肠癌预后。

Objective To evaluate the expression of vascular endothelial factor （VEGF）-D in predicting the prognosis of colorectal carcinoma （CRC）. Methods Between Jan 1996 and Jan 1998, 69 patients with CRC undergoing curative surgery were included in this study, Postoperative follow-up included physical examination, serum CEA, and imaging every 3 months in the first and the second year, every 6 months in the third year and once a year thereafter. The expression of VEGF-D protein and microvessel density （MVD） in 69 tissues of CRC and 20 normal colorectal tissues was examined by immunohistochemistry （IHC）. Results of IHC staining were quantified by Axioplan 2 imaging analysis system. Results VEGF-D protein expression in the cytoplasm was found in all of the CRC tissues and 25% （5/20） of normal tissues. The VEGF-D expression was much higher in tumor tissue than in the corresponding normal tissue （P 〈 0. 01 ）. The expression of VEGF-D protein significantly correlated with the patients＇ age （P =0. 013）, depth of tumor invasion （P =0. 013）, and lymphatic invasion （P =0. 028）. The VEGF-D expression was significantly correlated with MVD. Overall survival and disease free survival were significantly poorer in patients with higher VEGF-D expression level. Conclusions VEGF-D expression is up-regulated in CRC tissues, which is significantly correlated with the prognosis of CRC patients.