K-ras基因型与直肠癌术前放化疗后肿瘤病理消退的相关性研究

Correlation between K-ras genetype with tumor regression of rectal cancer after preoperative chemoradiotherapy

摘要:

目的：探讨K-ras基因突变是否可作为直肠癌术前放化疗后肿瘤组织病理消退的预测因子。方法：收集我院行术前放化疗的Ⅱ、Ⅲ期直肠癌患者46例，通过放化疗前活检石蜡包埋组织获取DNA样本，经PCR扩增后测序，明确K-ras基因第12、13密码子突变情况。根据Dwork’s直肠癌肿瘤消退分级标准评定放化疗后肿瘤组织的病理改变，将TRG2+3+4定义为肿瘤组织消退良好，TRG0+1肿瘤组织无明显消退。结果：46例患者中成功提取DNA 43例，K-ras基因突变15例（34.9%），其中第12密码子突变11例（73.3%），第13密码子突变4例（26.7%）。43例患者中TRG2+3+4者29例 （67.4%），TRG0+1者14例（32.6%）。K-ras基因突变组和野生组肿瘤组织消退良好者分别为66.7%和67.8%，2组相比差异无统计学意义（P=0.793）。结论：在K-ras基因突变型和野生型的直肠癌患者中，术前放化疗后直肠肿瘤病理消退程度无差异，K-ras基因突变不能作为直肠癌术前放化疗后肿瘤组织病理消退的预测因子。

Abstract:

Objective：To evaluate whether the presence of K-ras gene mutations is a useful tumor-response marker in patients with locally advanced rectal cancer treated with preoperative chemoradiotherapy. Methods：46 patients with locally advanced rectal cancer who were treated with preoperative chemoradiotherapy were enrolled. DNA was isolated from paraffin-embedded tissues before chemoradiotherapy amplified by PCR，and then sequenced in order to detect K-ras mutations in codons 12，13. Post-operative speci－mens were classified according to the Dwork’s tumor regression grading （TRG）. Good tumor regression was defined as TRG 2+3+4，insignificant tumor regression as TRG 0+1. Results：DNA was successfully extracted from 43 patients，K-ras mutation occured in 15 patients（34.9%），of which mutation in codon 12 occurred in 11 patients（73.3%），and mutation in，codon 13 occurred in 4 patients （26.7%）. 29 （67.4%） patients were graded as TRG 2+3+4，14（32.6%）as TRG 0+1. Pathologic response rates in K-ras gene muta－tion group and wild group were 66.7% and 67.8%，respectively，with no significant difference between two groups （P=0.793）. Con－clusions：There is no difference in the degree of tumor pathological regression after preoperative chemoradiotherapy for rectal cancer in the different K-ras genotypes，K-ras mutation status does not predict response to preoperative chemoradiotherapy.