胃癌微卫星不稳定性和抑癌基因杂合缺失

目的研究微卫星不稳和抑癌基因缺失在胃癌发生中的作用．方法采用ＰＣＲ为基础的方法，检测了５３例胃癌中６个微卫星标记突变及ＡＰＣ／ＭＣＣ和ＤＣＣ基因杂合缺失（ＬＯＨ）．结果胃癌微卫星不稳的检出率为３２１％（１７／５３）．７例（１３２％）为微卫星高频率不稳（３个以上微卫星标志），１０例（１８９％）为微卫星低频率不稳（１或２个微卫星标记）．肠型胃癌微卫星高频率不稳的发生率（２５０％）显著高于弥漫型胃癌（３４％）（Ｐ＜００５）．高频率不稳组未发现有ＡＰＣ，ＭＣＣ和ＤＣＣ基因ＬＯＨ，微卫星高频率不稳与ＡＰＣ／ＭＣＣ和ＤＣＣ基因ＬＯＨ呈负相关．结论微卫星不稳在部分胃癌，特别是肠型胃癌早期发生中起重要作用，高频率不稳胃癌与遗传性非息肉大肠癌有共同的特点．与此相反，低频率不稳和无不稳胃癌可能通过ＬＯＨ病理途径发生

Microsatellite instability and loss of heterozygosity of suppressor gene in gastric cancer

AIM To evaluate the relationship between microsatellite instability (MSI) and loss of heterozygosity (LOH) of tumor suppressor genes in gastric carcinomas. METHODS Six microsatellite loci and LOHs at APC, MCC and DCC were analyzed by polymerase chain reaction (PCR) based methods. RESULTS MSI was observed in 32 1%(17/53) of gastric carcinomas. Seven (13 2%) gastric carcinomas were MSI high (three loci or more) and 10(18 9%) were MSI low (one or two loci). The frequency of MSI high proved to be significantly higher in intestinal (25 0%) than indiffuse type of carcinomas (3 4%, P <0 05), None of the MSI high tumors demonstrated LOH at APC, MCC or DCC loci. There was a trend towards a negative association between MSI high status and LOH at APC, MCC and DCC locus. CONCLUSION MSI plays an important and early role in gastric carcinogenesis of a subset of gastric cancers, particularly in the intestinal type. The MSI high subset has features in common with hereditary non polyposis colorectal cancer. By contrast, MSI low and MSI negative cancers appear to develop through the LOH pathway.