The Relevance Between KRAS Gene And MSI In Sporadic Colorectal Cancer

Objective:In this study,we analyzed the clinical and pathological features of MSI-H CRC and low-frequency microsatellite instability(MSI-L)/MSS CRC by detecting the distribution of MSI in sporadic CRC.Under detecting MSI types,we detected KRAS gene mutations in the CRC,and analysed the correlation between the MSI and KRAS gene mutations.According to the KRAS gene mutations and MSI types,the CRC patients were divided into four groups: group A(wild-type KRAS gene&MSS/MSI-L);group B(wild-type KRAS gene&MSI-H);group C(gene mutant KRAS&MSS/MSI-L);group D(gene mutant KRAS&MSI-H)to analyse the clinical and pathological features.Methods:743 surgery paraffin tissue samples which were randomly selected from January 2015 to December 2016 in diagnosed patients with CRC who underwent surgical treatment surgical were used for this study.The data of the patients in our hospital were collected,including the basic information,clinical data of the patients and the detected results of KRAS gene after operation.We detected MMR proteins(MLH1,MSH2,MSH6 and PMS2)in CRC tumor tissues by using immunohistochemical method.Statistical analysis was performed using SPSS 20 software.Results:1 The distribution of MSI types in sporadic CRC: the incidence of MSI-H,MSI-L and MSS colorectal cancer were respectively 9.6%,1.6% and 88.8%.2 MSI-H CRC has the unique clinical and pathological features: MSI-H was higher among younger people and in the right colon(P<0.001)and a lower degree of differentiation features(P<0.001),had less lymph node metastasis(P=0.008),higher incidence of mucinous adenocarcinoma(P<0.001).The higher incidence in the phase I/II of TNM staging was found in the postoperative patients(P<0.001).MSS/MSI-L CRC was higher in rectum,higher incidence of adenocarcinoma and a intermediate degree of differentiation features(P<0.001).MSI-H was not associated with tumor invasion depth,tumor thrombus,distant metastasis and gender.3 KRAS gene mutation rate was 39.2% in CRC and codon 12 and 13 mutation rate was 30.1% and 8.3%,respectively.The p.G12 D was the most common mutation site and the mutation rate was 14.7%(109/743).The p.G13 D was the second common mutation site and the mutation rate was 7.9%.4 The relationship between the KRAS gene mutations and clinical and pathological features in CRC: KRAS gene had a higher mutation rate in female patients 44.4%(132/297)which was more obvious than in male patients 44.4%(132/297),and there was statistical difference.KRAS gene had higher incidence of mucinous adenocarcinoma 53.8%(84/156)(P<0.001).KRAS gene mutations was not obvious associated with age,tumor location differentiation,tumor invasion depth,tumor thrombus,lymph node metastasis,distant metastasis.5 There was no significant difference between KRAS gene mutation rate of MSI CRC and MSS CRC.But the mutation rate of codon 12 in MSS CRC was more than MSI CRC and the mutation rate of codon 13 was higher in MSI CRC than in MSS CRC and there was statistical difference.6 CRC patients were divided according to the KRAS gene mutations and MSI types and analyzed the clinical and pathological features between the four groups.The KRAS gene mutations of CRC patients had higher incidence of mucinous adenocarcinoma and a higher mutation rate in female patients and there was statistical difference.However,the KRAS gene mutations were not associated with gender and pathological style.Conclusions1 The incidence of MSI-H was 11.9% in sporadic CRC.MSI-H CRC had an unique clinical and pathological features.2 There was a high consistency between MSI types and protein expression of MMR,and the IHC method to detect MSI types had high sensitivity and specificity.3 The mutation rate of KRAS gene was 43.9% in sporadic CRC.KRAS gene mutations had a relationship with female,distant metastasis and pathological stage III/IV of CRC.4 There was no significant difference between KRAS gene mutation rate of MSI CRC with MSS CRC.And the mutation rate of codon 12 in MSS CRC was more than MSI CRC.