| Background and Aims MSI was to show the MMR system abnormal that finded in up to 90% of HNPCC and up to 15% of sporadic colorectal cancer, the character was decrease or increase of simple repeat sequence. To detect the microsatellite instability (MSI) in sporadic colorectal cancer,not only for screening the HNPCC but also can to choose chems plan and judge the prognosis, whether have the simple and inexpensive approach can predict the MS status remain unknown.According to the revised Bethesda guidelines, MSI-H phenotype cancer is a type of sporadic colorectal cancer with specific pathological features,age at diagnosis, gender and site, were obtained; various pathological features were observed by light microscope,find the pathological features of independent identifier for MSI-H;and to compare the pathological features between HNPCC and sporadic MSI-H Colorectal Cancer.Colorectal cancer(CRC)is one of the most common malignant tumor. Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant hereditary syndrome caused by mismatch repair gene (MMR) germling mutation, which suggested a high risk of cancer in all HNPCC patients,so to diagnose HNPCC patients is the important public health issue.The clinical diagnosis criteria of HNPCC baced on the cancer family history, nowadays the family scale miniaturize increasingly, a parts of HNPCC families would be lost using the criteria. Germ-line mutations in the mismatch-repair (MMR)genes lead to the development of hereditary nonpolyposis colorectal cancer(HNPCC),We assessed feasibility and efficiency of strategies for molecular screening to identify patients with the HNPCC. Materials and Methods1.We enrolled 150 sporadic colorectal cancer patients,14 cases of carcinomas were collected from HNPCC families patients by colonoscopy. age at diagnosis, gender and site, were obtained.2. Standard microsatellite loci (BAT25,BAT26,D2S123,D5S346,D17S250) were amplified by polymerase chain reaction(PCR)with fluorescent primers, and the PCR products were analyzed by GeneMapper software.3. Various pathological features(tumor grade, mucinous differentiation, histologic heterogeneity, Crohn's-like response) were observed by light microscope; the express of TILs (CD4+ and CD8+) was detected by immunohistochemistry.We use the SPSS 13.0 to carry out Logistic stepwise regression analysis. To compare the pathological features between HNPCC and sporadic MSI-H Colorectal Cancer.4. We enrolled 150 patients,genotyping of the tumor for microsatellite instability (MSI) and IHC ware the primary screening method,among patients whose screening results were positive for MSI and MMR proteins negative, we searched for germ-line mutations in the MLH1, MSH2 genes with the use of genomic sequencing.Results1. Among 150 sporadic colorectal cancer patients, right hemicolon cancers were 54, appendix cancers were 14, ascending colon cancers were 22, transverse colon cancers were 15; left hemicolon cancers were 96, decending colon cancers were 17, sigmoid colon cancers were 29, rectum cancers were 50; Among 14 HNPCC patients, right hemicolon cancers were 9, appendix cancers were 3, ascending colon cancers were 2, transverse colon cancers were 4; left hemicolon cancers were 5, decending colon cancers were 1, sigmoid colon cancers were 1, rectum cancers were 3.2. Among 150 sporadic colorectal cancer patients, MSI-H was 13.33%; MSI-L was 6.00%; MSS was 80.67%; Among 14 HNPCC patients, MSI-H was 71.42%; MSI-L was 14.29%; MSS was 14.29%.3. Independent identifier were poor differentiation,histologic heterogeneity, Crohn's-like reaction and tumor-infiltrating lymphocytes, The following logistic regression formula was was generated that could be used to predict the probability of a patient's tumor being MSI-H at a given poor differentiation and histologic heterogeneity and Crohn's-like reaction and tumor-infiltrating lymphocytes: P=A/A+1,A=exp(α+β1 poor differentiation +β2 histologic heterogeneity +β3 Crohn's-like reaction +β4TILs);α =-1.872,EXP(α)=0.154;β1=2.292,EXP(β1)=9.893;β2=3.205,EXP(β2)=24.649;β3=3.183,EXP(β3)=24.116;β4=4.407,EXP(β4)=82.043; logistic regression formula has a sensitivity of 70.0% and a specificity of 99.2% and a accurate ratio of 95.3% for MSI-H. The features of HNPCC were histologic heterogeneity and Crohn-like reaction and TILs and Contiguous traditional adenoma; the features of sporadic MSI-H Colorectal Cancer were age at diagnosis <50 years and female and proximal location and poor differentiation and mucinous differentiation and contiguous serrated adenoma.The features of female and TILs CD8+ and contiguous serrated adenoma has statistical significance.4. 22 were MMR proteins negative in 150 cancer, hMLH1 proteins negative was 10, hMSH2 proteins negative was 12; 18 were MMR proteins negative in MSI-H cancer,1 were MMR proteins negative in MSI-L cancer, 3 were MMR proteins negative in MSS cancer. 3 of these patients had a mutation causing the MMR mutation. To compare the MSI and the IHC find the well correspond with two methods.Conclusions1.MSI-H phenotype cancer is a type of sporadic colorectal cancer with specific pathological features, clinicopathological features can identify efficiently MSI-H colorectal cancers. Independent identifier were poor differentiation, histologic heterogeneity, Crohn's-like reaction and tumor-infiltrating lymphocytes, The logistic regression formula was was generated that could be used to predict the probability of a patient's tumor being MSI-H. There is some evidence that the two principal subtypes of MSI-H CRC evolve through different pathways.The sporadic MSI-H colorectal cancer has special pathological features.2.Use the molecular biology method can identify HNPCC effective, IHC has the same efficiency with MSI. The clinical diagnosis criteria of HNPCC baced on the cancer family history, nowadays the family scale miniaturize increasingly, a parts of HNPCC families would be lost using the criteria. |
