摘要
目的探讨mutL同源基因1(mutL homologous gene 1,MLH1)在胃癌患者中的表达及其对预后及术前新辅助化疗反应的预测价值。方法收集2010年1月至2016年12月期间在本院行胃癌根治术的323例胃癌患者为研究对象。采用免疫组化法检测MLH1的表达。根据存活癌细胞的比例评估术前化疗的组织学反应。在免疫组化结果MLH1阴性表达的肿瘤中评估MSI状态。采用Cox回归分析影响无复发生存期(recurrence-free survival,RFS)的独立危险因素。结果323例胃癌患者中,MLH1阴性表达32例(9.9%),阳性表达291例(90.1%)。32例MLH1阴性表达患者中,MSI-H27例(84.3%),MSS/MSI-L 5例(15.7%)。MLH1阴性组的化疗反应者比例低于MLH1阳性组(21.4%vs 60.4%,P<0.001)。未行术前新辅助化疗的患者(n=198)中,MLH1阴性组的RFS较MLH1阳性组长(P<0.001);在接受术前新辅助化疗的患者(n=125)中,两组RFS差异无统计学意义(P=0.352)。多因素Cox回归显示,MLH1阳性表达患者的复发风险较MLH1阴性表达患者高(HR=2.45,95%CI:1.06~5.67,P=0.037)。结论MLH1缺失与化疗耐药相关,不会延长新辅助化疗后的RFS,且MLH1与MSI状态高度相关,可能是MSI的替代指标。
Objective To investigate the expression of mutL homologous gene 1(MLH1)in patients with gastric cancer and its predictive value for prognosis and preoperative neoadjuvant chemotherapy response.Methods A total of 323 patients who underwent radical gastrectomy in Hainan Hospital of Traditional Chinese Medicine from January 2010 to December 2016 were collected as the research objects.The expression level of MLH1 was determined by immunohistochemistry.The histological response of preoperative chemotherapy was evaluated based on the proportion of surviving cancer cells.MSI status was evaluated in tumors with negative expression of MLH1 based on the results of immunohistochemistry.The Cox regression was used to analyze the independent risk factors affecting recurrence-free survival(RFS).Results Among the 323 patients,32(9.9%)had negative expression of MLH1 and 291(90.1%)had positive expression of MLH1.Among the 32 patients with MLH1 negative expression,27(84.3%)were MSI-H and 5(15.7%)were MSS/MSI-L.The proportion of neoadjuvant chemotherapy responders in the MLH1 negative group was lower than that in the MLH1 positive group(21.4%vs 60.4%,P<0.001).Among patients without preoperative neoadjuvant chemotherapy(n=198),the RFS of the MLH1 negative group was longer than that of the MLH1 positive group(P<0.001).Among patients who received preoperative neoadjuvant chemotherapy(n=125),there was no statistically significant difference in RFS between the two groups(P=0.352).Multivariable Cox regression showed that patients with MLH1 positive expression had a higher risk of recurrence than those with MLH1 negative expression(HR=2.45,95%CI:1.06-5.67,P=0.037).Conclusions MLH1 deletion is associated with chemotherapy resistance and the RFS after neoadjuvant chemotherapy is not prolonged.MLH1 is highly correlated with MSI status and can be a surrogate indicator of MSI.
作者
周高云
林龙
林进维
苏德文
ZHOU Gaoyun;LIN Long;LIN Jinwei;SU Dewen(Department of General Surgery,Hainan Hospital of Ttraditional Chinese Medicine,Hainan 570203,China)
出处
《中国癌症防治杂志》
CAS
2022年第1期65-69,共5页
CHINESE JOURNAL OF ONCOLOGY PREVENTION AND TREATMENT
基金
海南省自然科学基金项目(820QN408)。
关键词
胃癌
mutL同源基因1
微卫星不稳定性
预后
新辅助化疗
Gastric cancer
mutL homologous gene 1
Microsatellite instability
Prognosis
Neoadjuvant chemotherapy
