MSI和VEGF在NSCLC组织中的表达及临床病理相关性研究

Expression and clinicopathologic correlation of microsatellite instability and vascular endothelial growth factor in non-small cell lung cancer

目的:研究微卫星不稳定性和血管内皮生长因子在非小细胞肺癌中的表达及其之间的相关性。方法:应用PCR-变性聚丙烯酰胺技术检测94例非小细胞肺癌肿瘤组织及相应正常肺组织的D 3S1067、D 3S659、D 3S966及AR四个位点的微卫星不稳定性。采用免疫组织化学方法测定94例非小细胞肺癌病理切片中血管内皮生长因子的表达情况,并对二者与患者的年龄、性别、病理类型、组织分化程度、临床分期、淋巴结转移和生存时间相关性进行统计分析。结果:在所有病例中64.89%呈现至少一个位点的微卫星不稳定性阳性。微卫星不稳定性阳性组与阴性组相比较,其淋巴结转移率明显增高,差异有统计学意义(P<0.05)。血管内皮生长因子阳性率为62.8%,其基因的表达与肺癌患者的细胞分化程度、TNM分期、5年生存率和淋巴结转移状态密切相关(P<0.05)。微卫星不稳定性和血管内皮生长因子阳性患者的生存时间显著低于微卫星不稳定性阴性患者(P<0.05)。COX回归模型分析显示,微卫星不稳定性和血管内皮生长因子对非小细胞肺癌患者是一个重要的预后判断因素(P<0.01)。结论:微卫星不稳定性和血管内皮生长因子的表达与非小细胞肺癌的临床病理学特征密切相关,二者的检测将有助于肺癌的诊断,评估肺癌患者的恶性程度和预后。

Objective To study the microsatellite instability and vascular endothelial growth factor expression and its clinical significance in non-small cell lung cancer. Methods Ninety-four lung cancer specimens from non-small cell lung cancer were investigated. A very precise micro-dissection technique was used to obtain the genomic DNA from tumor tissue and paired normal tissue, followed with PCR amplification of 4 polymorphic genomic sequences （D3S1067, D3S659, D3S966 and AR）. The expression of vascular endothelial growth factor was detected with immunohistochemical staining. The relationship between the expression of vascular endothelial growth factor and microsatellite instability and the age, sex, histopathological type, differentiation, stage, lymph-node metastasis and survival time were analyzed statistically. Results Sixty-one （64.89 %） of non-small cell lung cancer patients showed microsatellite instability at single or multiple loci. Statistically significant correlation was found between microsatellite instability and lymph node metastasis （P 〈 0. 01）. Vascular endothelial growth factor expression in non-small cell lung cancer was 62. 8% （59/94）, the expression of vascular endothelial growth factor was significantly correlated with grade of cell differentiation, TNM stages, the five-year survival rate and lymph node status （P 〈 0. 05）. Microsatellite instability and positive vascular endothelial growth factor patients had significantly shorter survival time than microsatellite instability and negative vascular endothelial growth factor ones did （P〈0.05）. Cox-proportional-hazard-regression-model analysis confirmed that microsatellite instability and vascular endothelial growth factor were very important prognostic indicator for non- small cell lung cancer patients （P 〈0. 01 ）. Conclusion Microsatellite instability and vascular endothelial growth factor expression are significantly correlated with the clinical pathological characteristics in non-small cell lung cancer. Detection of microsatellite instability and vascular endothelial growth factor may be valuable for diagnosing lung cancer and evaluating malignancy extent and prognosis.