胃癌中hMSH2表达缺失对EGFR及KRAS基因突变影响的研究

The effect of h MSH2 expression loss on EGFR and KRAS gene mutations in gastric carcinoma

目的:探讨胃癌中hM SH2表达缺失对EGFR和KRAS基因突变的影响。方法:收集大连地区胃癌标本63例,所有患者均未经放疗或化疗。应用免疫组织化学方法检测63例胃癌标本和38例癌旁组织的hMSH2、EGFR和KRAS蛋白的表达情况;应用HRM技术检测其中58例胃癌标本的EGFR基因19-21外显子和KRAS基因2外显子的突变情况,筛选出的阳性标本应用DNA测序证实。结果:hM SH2表达缺失率在胃癌组为34.9%,显著低于癌旁组的60.5%(P=0.012);在III-IV期胃癌组为47.4%,显著高于I-II期胃癌组的16.0%(P=0.011)。58例胃癌标本中,hM SH2表达缺失组的EGFR突变率为10.5%,高于hM SH2表达组的2.6%(P=0.513);hM SH2表达缺失组的KRAS突变率为15.8%,高于hM SH2表达组的7.7%(P=0.623)。EGFR蛋白表达率在胃癌组为47.6%,显著高于癌旁组的26.3%(P=0.034);在淋巴结转移组为57.4%,显著高于无淋巴结转移组的18.8%(P=0.007);在Ⅲ-Ⅳ期胃癌组为57.9%,显著高于III期胃癌组的32.0%(P=0.044)。KRAS蛋白表达率在胃癌组为6 3.5%,显著高于癌旁组的36.8%(P=0.009);在Ⅲ-Ⅳ期胃癌组为73.7%,显著高于I-II期胃癌组的48.0%(P=0.038)。结论:hM SH2表达缺失的胃癌组织可能更易携带EGFR及KRAS基因突变;hM SH2、EGFR和KRAS蛋白表达的增加可能早于胃癌的发生;hM SH2表达缺失、EGFR和KRAS蛋白表达增加在胃癌的进展中发挥作用。

Objective： To detect the effect of h MSH2 expression loss on EGFR and KRAS gene mutations in gastric carcinoma（ GC）. Methods： A total of 63 specimens of GC operation were collected. All patients did not receive preoperative radiotherapy or chemotherapy. The expression of h MSH2,EGFR and KRAS proteins were detected by immunohistochemical method in 63 cases of GC and 38 cases of adjacent normal tissue. Mutations of EGFR exons 19-21 and KRAS exon 2 were detected by HRM in 58 GCs from these 63 ones. All mutations screened by HRM were verified by DNA sequencing. Results： The loss rate of h MSH2 expression was significantly lower in GC 34. 9% than adjacent normal tissue 60. 5%（ P = 0. 012）,significantly higher in GC with III-IV stage 47. 4% than I-II stage16. 0%（ P = 0. 011）. The EGFR mutation frequency was higher in h MSH2 expression loss GCs 10. 5% than in h MSH2 expression ones 2. 6%（ P = 0. 513）. The KRAS mutation frequency was higher in h MSH2 expression loss GCs15. 8% than in h MSH2 expression ones 7. 7%（ P = 0. 623）. The expression rate of EGFR protein was significantly higher in GC 47. 6% than adjacent normal tissue 2 6. 3 %（ P = 0. 0 3 4）,significantly higher in GC with lymph node metastasis 57. 4% than without lymph node metastasis 18. 8%（ P = 0. 007） and higher in GC with III-IV stage 57. 9% than I-II stage 32. 0%（ P =0. 044）. The expression of KRAS protein was significantly higher in GC 63. 5%than adjacent normal tissue 36. 8%（ P = 0. 009）,significantly higher in GC with III-IV stage 73. 7% than I-II stage 48. 0%（ P = 0. 038）. Conclusion： EGFR and KRAS mutations may be more frequent in h MSH2 expression loss GCs,h MSH2,EGFR and KRAS proteins expression may increase prior to GC occurrence,the loss of h MSH2 expression,the increase of EGFR and KRAS proteins may play roles in development of GC.