胃粘膜肠化生组织中p53、APC、K-ras基因突变的研究

Mutation of p53, APC and K-ras genes in different types of intestinal metaplasia of gastric mucosa

目的:探讨p53、APC及K-ras基因突变在不同类型肠化生癌变中的作用。方法:用PCR-SSCP及PCR-RFLP技术检测了47例肠化生组织中p53基因5-8外显子及APC基因15-6外星子、K-ras基因第12位点突变。结果:47例杨化生组织中p53突变14例，占29.8％，APC及K-ras基因突变各3例，分别占68％。场化生中Ⅰ、Ⅱ型肺化33例，Ⅲ型肠化14例（其中3例与Ⅱ型历化并存），Ⅲ型历化中p53突变率为57.1％（8／14），显著高于Ⅰ、Ⅱ型场化（18.2％，6／33，P＜0.05），而APC，K-ras基因在Ⅲ型肠化中的突变率（均为14.3％）虽也高于Ⅰ、Ⅱ型肠化（均为3.0％），但统计学检验无显著意义（P＞0.05）。1例Ⅲ型场化同时检出p53及K-ras突变.结论:不同类型历化生共分子改变机制有所不同，p53基因与Ⅲ型场化生的发生及癌变可能密切相关，并可能成为胃癌早期诊断的分子标志。

Objective: To investigate the role of the mutation of p53, APC and K-ras genes in different types of intestinal rnetaplasia (IM ) of gastric mucosa. Methods: Exons 5 to 8 of p53. exon 15-6 of APC and codon 12 of K-ras were examined for mutation with PCR-SSCP and PCR-RFLP in 47 cases of IM. Results:Mutation of p53, APC and K-ras genes was found in 29. 8% (14/47)6. 4% (3/47) and 6. 4% (3/47) respectively. IM was classified into type Ⅰ, type Ⅱ (33 cases) and type, (14 cases). The mutation rate of p53 gene was significantly higher in type Ⅲ IM(8/14) than in type I and type,Ⅱ (6/33)(P＜0. 05). The mutation rate of APC and K-ras was also higher in type, Ⅲ IM (2/14) than in type I and type Ⅱ IM(1/33) but there was no statistical significance (P＞0, 05). In one case of type Ⅲ IM, mutation of p53 coexisted with mutation of K-ras. Conclusion: The mechanism of molecular changes in 3 types of IM are different. The mutation of p53 may be closely related to carcinogenic degeneration and can possible be a marker of early diagnosis of gastric carcinoma.