结直肠腺癌中肿瘤出芽与KRAS、NRAS、BRAF基因突变、MSI状态的关系及临床意义  

Correlation of tumor budding with KRAS, NRAS, BRAF gene mutation andMSI status in colorectal adenocarcinoma and their clinical significance

作　　者：石娜 王康 周晓蝶 魏雪 丁康[3] 饶秋 SHI Na;WANG Kang;ZHOU Xiaodie;WEI Xue;DING Kang;RAO Qiu(Jinling Clinical Medical College of Nanjing Medical University,Nanjing 210002,China;Department of Pathology,Nanjing Traditional Chinese Medicine Hospital,Nanjing 210006,China;Department of Anorectal Surgery,Nanjing Traditional Chinese Medicine Hospital,Nanjing 210006,China)

机构地区：[1]南京医科大学金陵临床医学院,南京210002 [2]江苏省南京市中医院病理科,南京210006 [3]江苏省南京市中医院肛肠科,南京210006

出　　处：《临床与实验病理学杂志》2023年第11期1362-1367,共6页Chinese Journal of Clinical and Experimental Pathology

摘　　要：目的探讨结直肠腺癌中肿瘤出芽(BD)与KRAS、NRAS、BRAF基因突变、微卫星不稳定性(microsatellite instability,MSI)的关系及临床意义。方法收集237例结直肠腺癌的临床资料,判读BD。采用RT-PCR法检测229例KRAS、NRAS、BRAF基因突变,分析BD与基因突变的相关性。应用PCR法检测MSI,分析其与BD的关系。结果237例患者中低-中级别BD者147例,高级别BD者90例,BD与肿瘤最大径、脉管神经侵犯、组织学分化、淋巴结侵犯、癌结节形成、肿瘤复发、TNM分期均有关(P<0.05),与患者年龄、性别、发病部位均无关。淋巴结转移单因素Logistic回归分析显示:BD与淋巴结转移风险相关(P<0.05),多因素Logistic回归分析显示:BD是影响结直肠腺癌淋巴结转移的独立预测因素(P<0.05)。229例患者中KRAS突变率为42.4%,NRAS突变率为2.6%,BRAF突变率为3.1%。在KRAS、NRAS、BRAF突变患者中,高级别BD率分别为56.7%、33.3%、14.3%。BD与Kras12、Kras13密码子突变和KRAS总突变均有关(P<0.05),与NRAS、BRAF均无关。高级别BD中KRAS突变主要为Kras12、Kras13密码子突变。KRAS突变患者出现高级别BD,其无进展生存时间、总生存时间短(P<0.05)。237例患者中,MSI高度不稳定率为6.8%,16例MSI高度不稳定中仅2例为高级别BD,其与MSI呈负相关(r=-0.143,P<0.05)。结论结直肠腺癌中BD与Kras12、Kras13密码子突变、KRAS总突变、MSI状态均有关;BD也与结直肠腺癌预后相关,可为预后判断提供参考。Purpose To explore the clinicopathological relationship between tumor budding and KRAS,NRAS,BRAF gene mutations and MSI status in colorectal adenocarcinoma and their clinical significance.Methods The clinical data of 237 cases of colorectal adenocarcinoma were collected to interpret tumor budding.RT-PCR was used to detect the gene mutations of KRAS,NRAS,BRAF in 229 cases and to analyze the correlation between tumor budding and gene mutations.MSI was detected by PCR and its relationship with tumor budding was analyzed.Results Of the 237 patients,147 showed low-to medium-grade tumor budding and 90 showed high-grade tumor budding.Tumor budding was associated with tumor size,vascular involvement,perineural invasion,tumor differentiation,lymph node metastasis,tumor nodule formation,tumor recurrence and TNM staging(P<0.05),while it was not associated with age,sex and location.Single factor logistic regression analysis showed that tumor budding was associated with the risk of lymph node metastasis(P<0.05),while multivariate logistic regression analysis showed that tumor budding was an independent predictor of lymph node metastasis in colorectal adenocarcinoma(P<0.05).Of the 229 cases,the mutation rate of KRAS,NRAS and BRAF was 42.4%,2.6%and 3.1%,respectively.Among KRAS,NRAS and BRAF mutation cases,the proportion of high-grade tumor budding was 56.7%,33.3%and 14.3%,respectively.Tumor budding was associated with mutations in the Kras 12 and Kras 13 codons,as well as KRAS total mutations(P<0.05).However,tumor budding had no relationship with NRAS and BRAF.In the high-grade budding tumors,KRAS mutations were mainly KRAS codons 12 and 13.Among the cases with KRAS mutation,the disease-free survival time and total survival time of the cases with high-grade tumor budding were significantly shorter(P<0.05).Of the 237 patients,the rate of MSI-H was 6.8%and only 2 out of 16 MSI-H patients had high-grade tumor budding.There was a negative correlation between tumor budding and MSI status(r=-0.143,P<0.05).Conclusion Tumor budding is

关 键 词：结直肠肿瘤 肿瘤出芽 KRAS NRAS BRAF 微卫星不稳定 

分 类 号：R735.3[医药卫生—肿瘤]