胃癌p53基因突变与微卫星DNA不稳定性关系的研究  

Study on the p53 gene mutation and microsatellite instability of gastric carcinoma

作　　者：郭文[1] 张亚历[1] 吴保平[1] 张立力[1] 周殿元[1] 

机构地区：[1]第一军医大学南方医院消化科,广州510515

出　　处：《中华医学遗传学杂志》2000年第2期101-102,共2页Chinese Journal of Medical Genetics

摘　　要：目的　探讨术前不同分期的胃癌 p5 3基因突变与微卫星 DNA不稳定性 (microsatelliteinstability,MSI)的变化及其相互关系。方法　应用超声内境 (endoscopic ultrasonography,EUS)对 73例胃癌患者行术前分期 ,同时采用银染 PCR- SSCP方法检测内镜活检组织标本 p5 3基因突变及 MSI。结果　p5 3基因总突变率为 5 4.8% ;T3期 (6 4.3% )和 T4期 (6 7.9% )突变率明显高于 T1(0 )或 T2期 (2 5 .0 % )病例 (P<0 .0 5 ) ;有淋巴结转移的病例突变率为 6 7.6 % ,亦明显高于无转移时的 41.7% (P<0 .0 5 )。MSI总检出率为 37.0 % ;与癌的浸润深度无关 ,T1～ T4期癌 MSI的检出率分别为 40 .0 %、33.3%、39.3%和34 .5 % (P>0 .0 5 ) ;但有淋巴结转移组 MSI的检出率为 5 1.4% ,明显高于无转移的 2 2 .2 % (P<0 .0 5 )。 p5 3基因突变组 ,MSI检出率 (42 .5 % )较无突变组 (30 .3% )有增高趋势 ,但两者无显著性差异 (P>0 .0 5 )。结论　 p5 3基因改变与 MSI可能分别代表了胃粘膜癌变过程中的不同分子病理学机理 ,两者均不同程度地反映胃癌的细胞生物学恶性行为 ,对临床分析胃癌的预后可能有参考意义。Objective To observe the relationship between p53 gene mutation and microsatellite instability (MSI) of the preoperative staging of gastric carcinoma by endoscopic ultrasonography(EUS). Methods A total of 73 cases of gastric carcinoma were taken for the preoperative staging with EUS.Silver staining PCR SSCP method was used to detect mutations in exons 5,6,7,8 of p53 gene and MSI at 4 loci on chromosomes 2,5,17 in the 73 paraffin embedded biospy specimens, and the relationship between them was studied further.Results The overall mutated rate of p53 gene was 54.8%, with 6.8%, 15 1%, 19 2% and 13.7% in exons 5 to 8, respectively. Analysis of the relation of the mutation with the preoperative staging by EUS showed that it was significantly higher in T3(64.3%) and T4(67.9%) than in T1(0) or T2(25.0%)(P<0.05), and it was 67.6% in cases with lymph node metastasis, which was significantly higher than that without metastasis (41.7%)(P<0.05). The overall detective rate of MSI was 37.0%. The detective rate of MSI had no relation with the depth of invasion, which was 40.0%, 33 3%,39.3% and 34.5% at T1 to T4 stages(P<0.05),respectively, but it was significantly higher in cases with lymph node metastasis(51.4%) than those without metastasis(22.2%)(P<0.05).Although the detective rate of MSI showed an increasing trend in the mutated cases of p53 gene as compared with the no mutation cases,there was no relationship between MSI and p53 gene mutation (P<0.05).Conclusion These results suggest that the gene mutation of p53 and MSI may represent the different mechanisms of carcinogenesis.They can reflect the cytobiologic malignant behavior of gastric carcinoma in varying degrees, which may be of reference significance in analysing the prognosis of the patients in clinics.

关 键 词：胃癌 P53基因突变 微卫星DNA 不稳定性 

分 类 号：R735.2[医药卫生—肿瘤]