胃癌及胃液中p53、ras基因突变与临床病理的关系

Study of the relationship between clinicopathology and p53, ras gene mutation in gastric cancer and gastric juice

目的 :探讨胃良性病变向恶性转化过程中 p5 3、ras基因突变的规律 ,并分析胃癌无损伤基因检测的可行性。方法 :应用PCR SSCP及免疫组织化学方法对比研究。结果 :异型增生 p5 3基因突变率 10 % (3/30 )、ras基因突变率 16 7% (5 /30 ) (二者总突变率 2 6 7% ) ;早期胃癌p5 3基因突变率 35 % (7/2 0 )、ras基因突变率 6 0 % (12 /2 0 ) (二者总突变率 85 % ,其中 2例重复突变 ) ;中晚期胃癌 p5 3基因突变率 6 0 % (18/30 )、ras基因突变率 4 3 3% (13/30 ) (二者总突变率 90 % ,其中 4例重复突变 ) ;胃息肉ras基因突变仅 1/10。 30例胃溃疡边缘正常黏膜均未发现 p5 3、ras基因突变。p5 3基因突变的 2 5例胃癌的胃液中其相应的突变率 32 % (8/2 5 )。 19例胃癌患者的胃液中 9例有ras基因突变 4 7 1% (9/19)。异型增生 p5 3蛋白过度表达阳性率13 3% (4/30 ) ,p2 1ras蛋白阳性率 16 7% (5 /30 )。胃癌 p5 3蛋白阳性率 5 6 % (2 8/5 0 ) ,p2 1ras蛋白阳性率 6 0 % (30 /5 0 )。正常胃黏膜上皮、溃疡边缘正常黏膜及胃息肉均呈p5 3及ras蛋白阴性表达。结论 :胃癌的发生发展与癌基因ras与抑癌基因p5 3的突变有关 ,且两种基因同时检测 ,可覆盖绝大多数胃癌病例 ,提高了本项技术的可靠性 ,提供了胃癌无损伤基因?

Purpose To study the principle of p53 and ras gene mutation in the course of transformation form benign gastric diseases to malignant diseases. Methods Make a comparison between PCR SSCP and immunohistochemical method. Results In the 30 cases of gastric dysplasia, p53 mutation rate was 10%(3/30) and the rate of ras mutation was 16 7%(5/30)(the all mutation rate was 26 7%). The rate of p53 gene mutation in early gastric cancer was 35%(7/20) and the rate of ras gene mutation was 60%(12/20) (the all mutation rate is 85%). And in advanced gastric cancer,the rate of p53 mutation was 60%(18/30),the rate of ras mutation was 43 3%(13/30)(the all mutation rate was 90%). But in gastric polyp the ras gene mutation rate was only 10%(1/10). p53 or ras mutations were not found in 30 cases of peptic ulcer border. In the gastric juice of 25 gastric cancer cases with p53 mutation, the rate of p53 mutation was 32%(8/25), and in the gastric juice of 19 gastric cancer cases with ras mutation the rate of ras gene mutation was 47 1%(9/19). In the immunohistochemical group, within 30 cases of gastric dysplasia, p53 overexpression positive rate was 13 3%(4/30), p21 ras positive rate was 16 7%(5/30). Within 50 cases of gastric cancer, p53 positive rate was 56%(28/50),p21 ras positive rate was 60%(30/50) and in cases of normal gastric mucosa, peptic ulcer border, or polyp, p53 and p21 ras were both negative. Conclusion The results prove that mutation of ras gene and p53 gene is related to the development of gastric cancer, and the test of both genes may cover the majority of gastric cancer and provided evidences to the feasibility of harmless gene test of gastric cancer.