The Different Expressions Of Mismatch Repair Protein (hMLH1and HMSH2) In Golorectal Polyps And Sporadio Colorectal Cancer

ObjectiveColorectal cancer (colorectal cancer, CRC) have the highest incidence in NorthAmerica, Western Europe and other developed countries. In recent years itsincidence is increasing in Asia, originally our country had a relatively lowincidence of colorectal cancer, but with the lives of our peoplediet Westernization of habits in recent years, incidence and mortality ofcolorectal cancer also showed an increasing trend. The development of tumor isa complex dynamic process, which involving multiple factors、complex processof multi-step genetic changes, which including oncogene activation, tumorsuppressor genes inactivation, and micro-satellite instability (MSI). Researchhas shown that the MMR gene mutation is an important way of colorectal tumorgenesis, which hMLH1and hMSH2is the most important two mismatch repairgenes. Study found that95%of hereditary non-polyp sis colorectal cancer(HNPCC) has hMLH1or hMSH2gene mutations, also in the sporadic colorectalcancer (SCRC), which hMLH1and hMSH2gene mutation plays an importantrole. With the increased incidence of sporadic colorectal cancer, the relationshipof hMLH1and hMSH2gene mutations with colorectal cancer is gradually beingtaken seriously, but colorectal adenomas which recognized as a precancerouslesion for colorectal cancer, the study in this two gene mutations still less. As aprecancerous lesion of colorectal cancer, hMLH1and hMSH2gene in colorectaladenoma will have a certain mutation rate or not? The mutation rate of these twogenes in tubular adenoma and villous adenoma is whether have adifference? And which pathologic type of colorectal cancer has a higher possibleof hMLH1and hMSH2gene mutations are currently unknown. This study aimed to investigate the mismatch repair gene expression changes in colorectaladenoma in order to explore its role in the development of colorectal adenomasin the process of ascending colon cancer.MethodsIn this study, divided the colorectal polyps which according to the pathologicaltype into three groups, including group colorectal inflammatory polyp, groupcolon tubular adenomas, and group villous adenomas in the colon,Using theimmunohistochemical method to detect hMLH1protein and hMSH2proteinexpression and mutation in colon inflammatory polyps、colorectal adenomasand colorectal carcinoma, in order to understand the MMR gene mutation andthe differences in these tissues. To explore the relationship of MMR gene withcolorectal adenomas, and further understanding the correlation of hMLH1andhMSH2gene in the process of colorectal adenomas to colorectal cancer.ResultsThe hMLH1protein negative expression rate was4.76%incolon Inflammatory polyps,and hMSH2protein are expression100%,both hMLH1and hMSH2protein negative expression are unrelated with the age,gender, polyp number and polyp site. hMLH1protein negative expression rate inadenomatous polyps was21.02%; hMSH2protein negative expression rate inadenomatous polyps was8.92%, the both negative rate was5.10%, thecombined negative expression was24.84%. Both hMLH1and hMSH2proteinnegative expression are unrelated with the age, gender, polyp numberand polyp site, also negative with the proportion of polyps fluff.In sporadic colorectal carcinoma, hMLH1protein negativeexpression was27.27%,hMSH2protein negative expression was13.64%, bothnegative rate was4.55%, the total negative expression was36.36%.The negative rate of the two protein expression are unrelated with thepatient age, gender, the polyp number and location, but has a relationship to the degree of cancer differentiation (P <0.05), the lower the degree of cancerdifferentiation, the negative rate will be higher, and the degree of malignancywill be higher too.ConclusionsThe results of this paper show that in the inflammatory polyps、adenomatous polyps and colorectal carcinoma, the negative expression rate ofhMLH1and hMSH2proteins showing increasing trend, the difference hasstatistically significant. And in this three groups, the abnormal number ofhMLH1protein expression is much larger than which inhMSH2protein expression. The hMLH1and hMSH2gene protein expressionincreased gradually from inflammatory polyps, colorectal adenoma toadenocarcinoma, suggesting that the MMR gene mutation or dysfunctionstart as early as the adenoma stage, and with the increase of the degree ofmalignancy, the mutation frequency of MMR gene is gradually increased,suggesting that the mutation of MMR genes, especially hMLH1andhMSH2mutation may be an early event in colorectalcancer. In the three groups of specimensof tissue, the mismatchrepair expression missing mainly due to expression of hMLH1protein-based, suggesting thatthe loss of hMLH1protein expression plays an importantrole in the pathogenesis of colorectal cancer.