Correlation of tumor budding with KRAS,NRAS,BRAF gene mutation and MSI status in colorectal adenocarcinoma and their clinical significance / 临床与实验病理学杂志

ABSTRACT

Purpose To explore the clinicopathological re-lationship 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 corre-lation between tumor budding and gene mutations.MSI was de-tected by PCR and its relationship with tumor budding was ana-lyzed.Results Of the 237 patients,147 showed low-to medi-um-grade tumor budding and 90 showed high-grade tumor bud-ding.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 regres-sion analysis showed that tumor budding was an independent pre-dictor 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.A-mong 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 muta-tions(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 bud-ding 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 pa-tients had high-grade tumor budding.There was a negative cor-relation between tumor budding and MSI status(r=-0.143,P＜0.05).Conclusion Tumor budding is related to the muta-tions in the Kras 12 and Kras 13 codons,as well as total KRAS mutations and MSI status.Tumor budding is also related to the prognosis of patients with colorectal adenocarcinoma,which can provide a reference for their outcome judgment.