血管内皮生长因子及其受体Flt-1和KDR在原发性胆囊癌的表达及其与临床病理特征的关系

VEGF, Flt-1 and KDR mRNA and protein expression in primary gallbladder carcinoma and their correlation with primary gallbladder carcinoma clinicopathological characteristics

目的探讨血管内皮生长因子(VEGF)、Flt-1和KDR的表达与原发性胆囊癌临床病理特征的关系。方法对21例原发性胆囊癌和10例胆囊腺瘤样息肉新鲜组织标本采用逆转录-聚合酶链反应(RT-PCR)和免疫组织化学染色在mRNA和蛋白水平检测VEGF、Flt-1和KDR在原发性胆囊癌和胆囊腺瘤样息肉的表达情况,并分析VEGF、Flt-1和KDR免疫组织化学阳性表达的病例与胆囊癌肝浸润、淋巴转移、病理分级和Nevin分期等临床病理特征的相关性。结果在胆囊癌和胆囊腺瘤样息肉组织中VEGFmRNA阳性表达率为90.47%(19/21)和20%(2/10);Flt-1mRNA阳性表达率为71.42%(15/21)和0%(0/10);KDR mRNA阳性表达率为85.71%(18/21)和10%(1/10);两组差异有统计学意义(P<0.05)。免疫组织化学染色VEGF蛋白检测阳性表达率为80.95%(17/21)和20%(2/10);Flt-1蛋白阳性表达率为60.90%(13/21)和10%(1/10);KDR蛋白阳性表达率为76.19%(16/21)和10%(1/10),两组差异有统计学意义(P<0.05)。VEGF、Flt-1和KDR蛋白的阳性表达率在胆囊癌肝浸润、淋巴转移和NevinI V、V期组明显高于无肝浸润、无淋巴转移和NevinI、Ⅱ、Ⅲ期组(P<0.05),而在高、中和低分化组三者的阳性表达率无统计学意义(P>0.05)。结论原发性胆囊癌组织中VEGF、Flt-1和KDR在mRNA和蛋白水平均存在高表达,VEGF、Flt-1和KDR蛋白的阳性表达同胆囊癌肝浸润、淋巴转移和Nevin分期明显相关,但与病理分级无明显相关。

Objective To explore the VEGF, Flt-1 and KDR mRNA and protein expression in primary gallbladder carcinoma （PC, C） and their correlation with primary gallbladder carcinoma clinicopathological characteristics. Methods The VEGF, Flt-1 and KDR mRNA and protein expression in the fresh resected samples of 21 cases of primary gallbladder carcinoma and 10 cases of gallbladder adenomaous ployps （GAP） was deteched by RT-PCR and immunohistochemistry. The correlation between VEGF, Flt-1 and KDR protein positive expression in PGC and the clinicopathological characteristics of PGC was analysed as well. Results The VEGF mRNA positive expression rates in all PGC and GAP cases were 90.47 % （19/21） and 20 % （2/10）, the Flt-1 mRNA positive expression rates were 71.42 % （15/21） and 0 （0/10） and the KDR mRNA positive expression rates were 85.71% （18/21） and 10% （1/10）, respectively, with the difference being significant between PGC cases and GAP cases （P〈 0.05）.The VEGF protein positive expression rates of all PGC and GAP cases were 80.95% （17/21） and 20% （2/10）, the Flt-1 protein positive expression rates were 60.90% （13/21） and 10% （1/10） and the KDR protein positive expression rates were 76.19% （16/21） and 10% （1/10）, respectively, with the difference being significant between two groups （ P 〈 0.05 ）. The VEGF, Fit-1 and KDR protein positive expression rates in PGC cases with liver infiltration, lymphatic metastasis and Nevin Ⅳ and Ⅴ stages were significantly higher than those in the cases withou liver infiltration, lymphatic metastasis and Nevin Ⅰ, Ⅱ and Ⅲ stages of PGC （P 〈 0.05）. However, the positive expression rates of VEGF, Flt-1 and KDR protein had no difference among the high, middle and low differentiation of PGC eases （P 〉 0.05） ,Conclusion The VEGF, Flt-1 and KDR mRNA and protein were all overexpressed in the cases of PGC and the overexpressions of VEGF, Flt-1 and KDR protein were significantly correlated with PGC liver infiltration, lymphatic metastasis and Nevin IV and V stages, but not with the PGC pathological differentiation.