胃黏膜病变演化过程中c-met基因表达改变及临床意义

目的：研究胃黏膜病变演化及细胞癌变过程中c-met基因表达改变及临床意义。方法：采用PCR－PCR－SSCP方法检测c-met原癌基因在肠型胃癌中的突变情况。利用组织微阵列技术对胃黏膜细胞癌变过程中c-met基因的表达水平进行检测。结果：以c-met基因的3个突变热点17、18和19外显子侧翼序列设计引物，扩增32例肠型胃癌及癌旁组织标本，PCR－SSCP未检测到有异常突变带型。154例胃镜活检组织标本中c-met蛋白阳性表达在30例浅表性胃炎为6例，阳性率为20％，在33例萎缩性胃炎中有8例，阳性率为24．2％。过表达率分别为10％和12．1％，两组间经统计检验P＞0．05，无统计学意义。肠化及异型增生的阳性表达强度也主要为弱阳性及中等强度阳性，其中4例中重度肠化生和3例中重度及1例轻度异型增生出现强阳性表达。6例肠化和6例异型增生为中等强度表达。c-met阳性表达在31例肠化中有17例，阳性率为54．8％，在30例异型增生中有17例，阳性率为56．7％。过表达率分别为32．3％和33．3％。在胃癌主要是中等强度和强阳性表达。包括6例中高分化腺癌，4例低分化腺癌，阳性率为53．3％，过表达率33．3％。肠化、异型增生和胃癌3组间阳性表达率经统计检验P＞0．05，无统计学意义。但3者阳性率均明显高于单纯的浅表性胃炎和萎缩性胃炎P＜0．05。过表达率在肠化、异型增生、胃癌中增高，但与责任中单纯的慢性胃炎相比未见统计学意义。结论：c-met基因在肠型胃癌中的变化方式是以过表达和基因扩增为主；c-met基因在胃黏膜病变演化及细胞癌变过程中表达及过表达呈上升趋势，从肠化开始即有明显增高，提示肠化具有癌前病变性质，应予以密切随访；组织阵列分析技术可作为高通量的技术进行基因表达的筛查。

Detection of c-met Oncogene Mutation and Expression in Intestinal Type Gastric Carcinoma

Objective:To determine c met oncogene changes and clinical significance in intesinal type gastric carcinoma.Methods:We chose exon 17,exon18 and exon 19 of c met gene and detected their mutation in 32 tumor specimens of intestinal type gastric carcinoma by performing analysis of PCR and PCP-SSCP techiques.Expression of c met gene was examined by tissue micro array technique.The materials comprised 154 gastric biopsy specimens with superficial gastritis,chronic atrophic gastritis,intestinal metaplasia,dysplasia and carcinoma taken from a natural population at high risk for gastric cancer.Results:Our data demonstrated that none point mutation was detected in exon 17,exon 18 and exon 19 of c met gene.The accumulation rate of c met protein in superficial gastritis,chronic atrophic gastritis,intestinal metaplasia,dysplasia and carcinoma was respectively 20%,24.2%,54.8%,56.7% and 53.3%.The rate of overexpression was respectively 10%, 12 1% ,32.3%,33.3% and 33.3%.The accumulation rate of c met protein in intestinal metaplasia,dysplasia and carcinoma was significant higher than superficial gastritis and chronic atrophic gastritis(P<0.05).The rate overexpression of c met protein in intestinal metaplasia,dysplasia and carcinoma was higher than superficial gastritis and chronic atrophic gastritis(P>0.05).Conclusion:The result showed that the point mutation of c met gene is not the main pattern of alteration in intestinal type gastric carcinoma.The rate expression and over expression of c met protein in intestinal metaplasia,dysplasia and carcinoma was higher than that in superficial gastritis and chronic atrophic gastritis.Intestinal metaplasia may have a higher risk of human gastric cancer.Tissue micro array is a high throughput screening strategy for mutation detection and protein expression.