| ObjectiveColorectal cancer(CRC)is one of the most commonly happened malignant tumors.The incidence rate and the mortality rate have been high,the incidence rate of CRC can be ranked third,the mortality rate ranked fifth in our country.The occurrence and development of CRC is a complex process involving multiple genes.Microsatellite instability(MSI)caused by mismatch repair genes(MMR)is an important reason leading to the development of CRC.Six mismatch repair genes have been cloned in human cellsat present,including human MutL homologue 1(hMLH1),human MutS homologue 2(hMSH2),human MutS homologue 3(hMSH3),human MutS homologue6(hMSH6),human postmeiotic segregation Increased 1(hPMS1),human postmeiotic segregation Increased 2(hPMS2).Mutations in any of these genes would result in defects in the mismatch repair function of the cells,which may lead to genetic alterations,characterized by MSI.Deletion of mismatch repair genes leads to decrease of the length and the number of repeats in the genome,resulting in the emergence of genetic instability.,There are some certain differences between tumor cells and normal cells on the microsatellite length and the number of repeats,that is,if mutation occurrence in the process of DNA replication will lead to MSI.Some scholarssuggest that MSI may become a risk factor for the prognosis of patients with CRC and they also suggest that patients with MSI have special clinicalpathologic features.This study was aims to investigate the relationship between the expression of hMLH1,hMSH2 and hMSH6 in CRC.The relationship betwwen their expression and CRC clinicopathological characteristics was also analyzed.This study may shed new light on investigating the clinical significance of MSI in CRC,and MSI may be highlighted as cancer new diagnostic method and therapeutic target of CRC patients.MethodsThis study selected cases in the Fourth People's Hospital of Jinan from March 24,2010 to December 24,2015.We obtained sixty cases at last.All the patients were diagnosed in pathological level and given radical surgery,none of them were given neoadjuvant radiotheraphy and neoadjuvant chemotheraphy.All the patients were given FOLFOX after surgery.Took out the tumor specimens from all there patients,preparation to pathological section,and detected hMLH1?hMSH2 and hMSH6 DNA mismatch repair protein expression by immunohistochemistry.According to DNA mismatch repair protein expression,microsatellite instability of tumor was classified as three types.If above two of three repair protein didn't express,we call it microsatellite instability-high(MSI-H).If only one of three repair protein didn't express,we call it microsatellite instability-low(MSI-L).If all of three repair protein expressed,we call it microsatellite stable(MSS).We recorded clinicalpathologic information of all there patients,and followed up all there patients at least two times.Follow-up mode: out-patient follow-up review,inpatient medical records,telephone follow-up review.The main contents included: survival status,recurrence and metastasis,cause of death,postoperative chemotherapy.Follow-up time: from the date of the pathological diagnosis of colorectal cancer to March 21,2016 or to the date of postoperative recurrence or to the date of death after the operation or lost to date.We see it complete data if patients appeared recurrence and metastasis or died of disease progression;and we see it censored data if patients lost halfway or died of other disease or followed up cutoff.Consulting the literature from at home and aboard and combining the clinical condition,we chosed clinicalpathologic features(gender,age,disease place,clinical stage,depth of tumor invasion,lymph node metastasis,differentiation degree,pathological type)to analyse of there sixty patients.The clinical and pathological features of 60 cases of patients with colorectal cancer were analyzed by chi-square test.The relationship betwwen expression of hMLH1,hMSH2,hMSH6 and CRC clinicopathological characteristics was analyzed.The relationship betwwen microsatellite instability and CRC clinicopathological characteristics was also analyzed.Correlation was analysed by using nonparametric Spearman rank correlation test.We made multivariate analysis performed bu Cox proportional hazard model in sixty CRC patients who were given FOLFOX after surgery to find out independent prognostic determinants.Using Kaplan-Meier method and Log-rank test to find out median-survival time of disease-free survival.All tests were performed at the 0.05 level of significances.Result1.The deletion rate of hMLH1 in 60 cases of colorectal cancer was 53.3%(32/60),and the deletion rate of hMSH2 was 33.3%(20/60),and the deletion rate of hMSH6 was 43.3%(26/60).The expression of hMLH1/hMSH2 deletion rate was 26.7%(16/60),the expression of hMLH1/hMSH6 deletion rate was 26.7%(16/60),the expression of hMSH2/ hMSH6 deletion rate was 23.3%(14/60),the expression of hMLH1/hMSH2/hMSH6 deletion rate was 18.3%(11/60).2.The hMLH1 deletion rate was related with pathological type(?2=5.249,P=0.022),but not with gender,age,disease place,clinical stage,depth of tumor invasion,lymph node metastasis,differentiation degree(P>0.05).The hMSH2 expression missing rate was related with pathological type(?2=4.342,P=0.037),but not with gender,age,disease place,clinical stage,depth of tumor invasion,lymph node metastasis,differentiation degree(P> 0.05).The hMSH6 deletion rate wasn't related with gender,age,disease place,clinical stage,depth of tumor invasion,lymph node metastasis,differentiation degree,pathological type(P > 0.05).3.hMLH1,hMSH2 protein expression was positively correlated with expression missing in colorectal cancer(r =0.378,P=0.003).hMSH2,hMSH6 protein expression was positively correlated with expression missing in colorectal cancer(r=0.381,P=0.003).hMLH1,hMSH6 protein expression deletion had no significant relationship(P> 0.05).4.The MSI-H,MSI-L and MSS in the tumor tissues from 60 patients were 60%(36/60),31.7%(19/60),28.3%(17/60),respectively.MSI-H was good in the right colon(?2=6.279,P=0.043),Mucinous adenocarcinoma(?2=6.025,P=0.049).Howerer,there was no significant difference in gender,age,clinical stage,depth of tumor invasion,lymph node metastasis,differentiation degree between the three groups: gender(?2=0.781,P= 0.677)age(?2=2.71,P=0.258)clinical stage(?2=1.395,P=0.498)depth of tumor invasion(?2=0.951,P=0.622)lymph node metastasis(?2=1.395,P=0.498)differentiation degree(?2= 0.881,P=0.644).5.MSI-H and MSS from 35 patients with ? stage colorectal cancer,there disease-free survival was significantly longer than that in patients with MSI-L(?2=10.751,P=0.005);MSI-H and MSI-L from 25 patients with ?I stage colorectal cancer,there disease-free survival was significantly longer than that in patients with MSS(?2=16.663,P=0.000);MSI-H from 60 patients with ?/?I stage colorectal cancer,there disease-free survival was significantly longer than that in patients with MSI-L /MSS(?2=7.994,P=0.018).Multivariate analysis revealed that lymph node metastasis(P=0.013),MSI(P=0.018)were independent prognostic factors of DFS in patients with colorectal cancer.Conclusion1.hMLH1,hMSH2,hMSH6 may play an important role in the occurrence of colorectal cancer,and the combined detection of colorectal cancer may have some reference value in diagnosis and treatment of colorectal cancer.2.Compared with MSI-L and MSS,MSI-H colorectal cancer patients have unique clinical and pathological features and have a relatively good prognosis.Concrete as follows: MSI-H is good in the right colon,Mucinous adenocarcinoma;MSI-H from sixty patients with ?/?I stage colorectal cancer,there disease-free survival was significantly longer than that in patients with MSI-L /MSS.Detection of MSI status is very important for improving the level of colorectal cancer treatment and improving the prognosis. |
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