摘要
目的:研究胃癌淋巴管生成与淋巴结转移的关系。方法:应用逆转录-聚合酶链反应(RT-PCR)和免疫细胞化学方法检测血管内皮生长因子-C(VEGF-C)和血管内皮生长因子受体-3(VEGFR-3)mRNA及其蛋白在5株胃癌细胞株和3对伴有淋巴结转移的胃癌组织及相应的正常黏膜中的表达。此外,还应用免疫组织化学方法检测86例胃癌标本的淋巴管密度(LVD)和VEGF-C蛋白的表达。结果:VEGF-C mRNA和蛋白高表达于3株胃癌细胞,而VEGFR-3 mRNA和蛋白在上述3个细胞株中均呈弱表达。VEGF-C和VEGFR-3 mRNA均表达于3对伴有淋巴结转移的胃癌和相应的正常黏膜组织中,但在正常组织中的表达水平低于肿瘤组织。VEGF-C蛋白在66.3%(57/86)的病例中呈阳性表达。在伴淋巴结转移的胃癌中,VEGF-C表达较无淋巴结转移者更显著(P<0.001),其表达与淋巴管浸润(P<0.001)和TNM分期(P<0.01)均密切相关,但与病人的年龄和性别、肿瘤大小、位置、组织学类型、浸润深度及远处转移均无明显相关。LVD则与VEGF-C蛋白表达(P<0.001)、淋巴结转移(P<0.01)、淋巴管浸润(P<0.01)、TNM分期(P<0.05)及组织学类型(P<0.05)密切相关,但与病人的年龄和性别、肿瘤大小、位置、浸润深度及远处转移无明显相关。结论:在胃癌中,VEGF-C可能通过VEGFR-3信号通道促进淋巴管生成,从而增加胃癌淋巴结转移率。因此,肿瘤淋巴管生成可能成为治疗胃癌的一个新靶点。
Objective To investigate the Mationship between lymphangiogenesis and lymph node metastasis in gastric carcinoma. Methods The expression of VEGF-C mRNA and protein in 5 gastric carcinoma cell lines was examined by reverse transeription-polymerase chain reaction (RT-PCR) and inununohistochemistrv. Simuhaneously, tumor specimens from 3 gastric carcinoma patients with lymph node metastasis paired with their corresponding normal mucosa were examined to verify VEGF-C and VEGFR-3 mRNA expression by RT-PCR. In addition, lylnphatic vessel density (LVD) (using an antibody staining podoplanin, a specific marker for lymphatic endothelium) and the expression of VEGF-C protein in tumor tissues of 86 patients with gastric carcinoma were studied hv imnmnohistochemistry. Results Three of the 5 gastric carcinoma cell lines, ie MKN-45. SGC-7901 and AGS. expressed VEGF-C mRNA and protein; VEGFR-3 mRNA and protein were also fairly expressed in above-me,tioned three cell lines. VEGF-C and VEGFR-3 mRNA expression was detected in all gastric earcinonms tissues with lymph node metastasis, and their corresponding normal mueosa tissues but the expression level in corresponding normal tissues was lower than that in tumor tissues. VEGF-C protein was expressed in 66.3% (57/86) of patients. VEGF-C protein expression was more frequently found in tumors with lymph node metastasis than in those without (P〈0.001). VEGF-C protein expression was also closely related to lymphatic invasion (P〈0.001) and TNM staging (P〈0.01). However, there was no significant correlation between VEGF-C expression and age and gender of patients, tumor size, tumor location, histological type. depth of invasion, and distant metastasis. LVD was associated with VEGF-C protein expression (P〈0.001), lymph node metastasis (P〈0.01). lymphatic invasion (P〈0.01). TNM staging (P〈 0.05). and histological type (P〈0.05). However, there was no significant correlation between LVD and age and gender of patients, tumor size
出处
《外科理论与实践》
2005年第5期404-408,共5页
Journal of Surgery Concepts & Practice
基金
上海市科委基金项目(044119664)
关键词
胃肿瘤
血管生长因子
肿瘤转移
淋巴管生成
Gastric neoplasms
Vascular endothelial growth factor
Lymph node metastasis
Lymphangiogenesis