摘要
目的:探讨散发结直肠癌组织微卫星不稳定性与错配修复基因hMHL1和hMSH2蛋白表达的关系。方法:结直肠癌患者病理标本和正常肠壁组织(距肿瘤边缘10cm取材各40例)。选取微卫星位点(D2S123、BAT-26、D17S261、D17S799)进行PCR,PCR产物行毛细管电泳法检测。用免疫组化染色方法分析错配修复基因hMHL1和hMSH2在肿瘤组织的蛋白表达情况。结果:1)4个位点(D2S123、BAT26、D17S261、D17S799)的微卫星不稳定性检出率分别为:12.5%、17.5%、10%、7.5%。总的微卫星不稳定率为9/40(22.5%)。MSI-H表达为7例,均表现BAT26位点不稳定。MSI-L表达2例。2)所有标本错配修复基因hMSH2检测均正常表达。错配修复基因hMHL1表达阴性11份,结肠比直肠hMLH1蛋白的阴性表达率高(P<0.01)。3)hMLH1表达阴性,是出现MSI的重要分子因素,hMLH1不表达和MSI相关显著(P<0.01)。结论:1)错配修复基因突变引起微卫星不稳定性是散发性结肠癌发生的重要机制;2)部分微卫星不稳定性是由错配修复基因hMLH1不表达引起,其余的微卫星不稳定性可能涉及到其它错配修复基因。
Objective: To nvestgate the retatonsh p between microsateilite instability(MSI)and mismatch genes hMHL1 and hMSH2 in sporadic colorectal cancer.Methods: Our research objects are patho og c spec mens from colorecta cancer pat ents the control from the normal intestinal wall tissue (10cm away from the tumor edge based). And the microsatellite toci(D2S123, BAT - 26, D17S261, D17S799) were studied by polymerase chain reaction (PCR), then the product were de- tected in Capillary electrophoresis. Analysis the protein expression of mismatch repair gene hMHL1 and hMSH2 in tumor tissues by staining method, Results:1) The microsatellite instability detection rate of 4 Ioci(D2S123, BAT26, D17S261, D17S799) is 12.5%, 17.5%, 10% and 7.5%, respectively. The total microsatellite unstable rate is 9/40 (22.5%).There are 7cases are MSI-H, and all the unstable site is BAT26,and 2cases are MSIL. 2) The hMSH2 mismatch repair gene are normal expression in all specimens. The negative expressio ,n of mismatch repair genes hMHL1 are 11 cases. Colon higher negative expression rate of hMHL1 protein (P〈0.01). 3) The negative expression of hMHL1 is one of the important molecular factors in MSI, and the two correlate significantly(P〈0,01). Conclusion: 1) MS/caused by mutation of mismatch repair genes Is an im- portant factor in the development of SRC. 2) Some of MS/are caused by the mutation of mismatch repair genes hMSH1, the rest of MSI may be correlated with other mismatch repair genes.
出处
《中国现代普通外科进展》
CAS
2015年第10期775-779,共5页
Chinese Journal of Current Advances in General Surgery