大肠癌KRAS/BRAF突变、微卫星不稳定及P53异常表达与肿瘤病理特征的关系  

The relationship between KRAS/BRAF mutations,microsatellite instability status,and abnormal P53 expression patterns with pathological characteristics in colorectal cancer

作　　者：杨泽然[1] 马杰[1] 叶美华[1] Yang Zeran

机构地区：[1]浙江省人民医院(杭州医学院附属人民医院),310014

出　　处：《浙江临床医学》2025年第2期172-175,共4页Zhejiang Clinical Medical Journal

基　　金：浙江省医药卫生科技计划项目(2021KY515)。

摘　　要：目的分析大肠癌中KRAS/BRAF突变、微卫星不稳定及P53异常表达模式与肿瘤病理特征之间的关系。方法回顾性分析247例接受根治性手术的大肠癌患者的临床病理资料,探讨大肠癌KRAS/NRAS/BRAF突变、微卫星不稳定状况和P53表达模式等分子表型特征,并分析这些特征与肿瘤黏液分化(>5%的细胞外黏液)、淋巴转移及TNM分期等病理特征的相关性。结果在大肠癌中,伴黏液分化的肿瘤占19.0%,其KRAS、BRAF突变和/或高频微卫星不稳定性(MSI-H)等异常分子表型检出率为74.5%,显著高于经典型大肠腺癌(<5%的细胞外黏液)的39.5%(P<0.05)。伴黏液分化的大肠癌显示较高的P53野生型表达模式检出率(P<0.05)。单变量分析表明,KRAS突变(OR=1.98,95%CI:1.04~3.76,P<0.05)、BRAF突变(OR=7.17,95%CI:1.94~26.55,P<0.01)和MSI-H表型(OR=4.35,95%CI:1.58~11.99,P<0.01)显著增加了伴黏液分化大肠癌的风险。这些相关性在考虑肿瘤部位、性别和年龄的多因素分析中差异具有统计学意义。P53异常表达模式在淋巴转移组和高TNM分期组中的检出率分别为67.6%和66.7%,明显高于无淋巴结组和低TNM分期组(分别为47.5%和48.3%)(P<0.05)。多变量分析显示,P53异常表达模式显著增加左半结肠癌淋巴转移风险(OR=2.60,95%CI:1.24~5.43,P<0.05)和高TNM分期风险(OR=2.23,95%CI:1.06~4.72,P<0.05),而MSI-H表型则显著降低了这些风险(OR=0.21,95%CI:0.04~0.98,P<0.05;OR=0.18,95%CI:0.04~0.84,P<0.05)。结论伴黏液分化的大肠癌与高频KRAS、BRAF突变、MSI-H表型和P53野生型表达模式正相关;P53异常表达模式显著增加了左半结肠癌淋巴转移和高TNM分期的风险。Objective To analyze the relationship between KRAS/BRAF mutations,microsatellite instability status,and abnormal P53 expression patterns with pathological characteristics in colorectal cancer.Methods A retrospective analysis of clinical and pathological data from 247 patients with colorectal cancer who underwent curative surgery was conducted.The molecular phenotype characteristics of colorectal cancer,including KRAS/NRAS/BRAF mutations,microsatellite instability status,and P53 expression patterns,were explored,and their correlations with pathological features such as tumor mucinous differentiation(>5%extracellular mucin),lymph node metastasis,and TNM staging were analyzed.Results In colorectal cancer,tumors with mucinous differentiation accounted for 19.0%,with a detection rate of 74.5%for abnormal molecular phenotypes such as KRAS,BRAF mutations,and/or high-frequency microsatellite instability(MSI-H),significantly higher than the 39.5%rate in classical-type colorectal adenocarcinoma(<5%extracellular mucin)(P<0.05).Tumors with mucinous differentiation in colorectal cancer showed a higher detection rate of P53 wild-type expression patterns(P<0.05).Univariate analysis indicated that KRAS mutations(OR=1.98,95%CI:1.04~3.76,P<0.05),BRAF mutations(OR=7.17,95%CI:1.94~26.55,P<0.01),a nd MSI-H phenotype(OR=4.35,95%CI:1.58~11.99,P<0.01)significantly increased the risk of colorectal cancer with mucinous differentiation.These correlations remained significant in a multivariate analysis that included tumor location,gender,and age as covariates.The detection rate of abnormal P53 expression patterns in the lymph node metastasis group and the high TNM staging group was 67.6%and 66.7%,respectively,significantly higher than in the lymph node negative group and the low TNM staging group(47.5%and 48.3%,respectively)(P<0.05).Multivariate analysis showed that abnormal P53 expression patterns significantly increased the risk of lymph node metastasis in left-sided colon cancer(OR=2.60,95%CI:1.24~5.43,P<0.05)and high TNM staging risk(OR

关 键 词：黏液腺癌 大肠癌 黏液分化 KRAS BRAF 微卫星不稳定 病理学 P53 表达模式 

分 类 号：R735.34[医药卫生—肿瘤]