Experimental Study Of Microsatellite Instability In Hereditary Nonpolyposis Colorectal Cancer

Objective To study the incidence of mierosatellite instability(MSI) in hereditary nonpolyposis colorectal cancer(HNPCC) families and suspected HNPCC families collected from population in Yunnan. Compare the difference of the clinicopathological features between the MSI positive families and the negative based on different clinical criteria.Identifythe relationship its clinicopathological feature,and to explore its to identify the kindreds with hereditary nonpolyposis colorectal cancer and to analyse its value and significance in clinical practice.Method1 13 HNPCC families fulfilling Amsterdam Criteria, a total of 30 cases of patients and 18 suspected HNPCC families, a total of 30 cases of patients, which diagnosis and surgical treatment after the clinicopathological material complete patient pedigree in the First affiliated hospital of kunming medical college,Tumor Hospital of Yunnan,People's Hospital of Dali state,People's Hospital of Honghe state were collected. All colorectal cancer patients tissue specimens from paraffinembedded tumor tissue and surrounding normal tissue and Fresh tumor tissue and surrounding normal tissue, the samples were confirmed colorectal cancer by biopsy or the pathological diagnosis after surgery. All patients had not received preoperative chemotherapy and radiotherapy.2 MSI was detected in the specimens by means of PCR-SSCP from collect tissue specimens(including tumor tissue and surrounding normal tissue) and paraffinembedded tumor tissue and surrounding normal tissue of operative patients,and extract DNA. Five microsatellite loci including BAT-25,BAT-26,D5S346,D2S123 and D17S250 were used. Results 1 The average age of cancer onset in thirty individuals from 13 families met the Amsterdam criteria(44.8), and the average age of cancer onset in thirty individuals from 18 suspected HNPCC families(53.2).2 Thirty individuals from 13 families met the Amsterdam criteria, the MSI-positive is 93.33%. Out of them,23 cases(76.67%) were MSI-H,5 cases (16.67%) were MSI-L and 2 cases(6.67%) were MSS. Bat25 and Bat26 among four loci showed MSI-H 95.65% and 100% respectively. Tumor occurrence position by the right half colon majority. The most pathologic type was tubular adenocarcinomas with moderately differentiation.3 Thirty individuals from 18 suspected HNPCC families, the MSI-positive is 26.67%. Out of them,5 cases(16.67%) were MSI-H,3 cases (10.0%) were MSI-L and 22 cases(73.33%) were MSS. Bat25 and Bat26 among four loci showed MSI-H 60.0% and 80.0% respectively. Tumor occurrence position disorder. This study team patients by rectal cancer majority. Pathologic type was mucus adenocarcinomas with Poorly differentiation.4 13 families of group AC versus 18 families of group suspected HNPCC:In 13 families of group AC,9 cases(39.13%) of multiple primary cancers in 23 patients with MSI-H positive were found, including 3 cases were synchronous extracolorectal relative tumours,6 cases were metachronous extracolorectal relative tumours. in 4 patients with MSI-L positive were not found multiple primary cancers.Out of them,5 cases of gastric cancer,endometrial carcinoma in 4 cases,2 cases of ovarian cancer,bladder cancer in one cases.The subset of patients, with better prognosis. In 30 families of group suspected HNPCC have not found multiple primary cancers. The subset of patients, with poor prognosis.Conclusion 1. This study showed incidence of hereditary colorectal caneer with familial predisposition in YunNan was higher. The trend of colorectal cancer incidence was gradually young, Genetic factors may play a important role, we need to increase awareness of young colorectal cancer and strengthen early detection and prevention to hereditary colorectal cancer patients.2. MSI can be used to detect MSI-positive expression in suspected HNPCC and HNPCC. High-frequency of MSI-positive was demonstrated with 93.33% in 13 families of group HNPCC. High-frequency of MSS and low-frequency of MSI-positive was demonstrated with 26.67% in 18 families of group suspected HNPCC respectively, The incidence of MSI-positive was higher in HNPCC than in sporadic HNPCC.3. This indicate the suspected HNPCC families had similar clinicopathological features as the HNPCC families need test the MSI, It is helpful to better clinical screening HNPCC families and early diagnosis tumor biological behavior and predicting prognosis of colorectal carcinomas, avoid the misdiagnosis of HNPCC patients. The detection of MSI can provide better indicators of screening the kindreds with HNPCC in the molecular level.There showed MSI testing plays a important role in the screening the kindreds with HNPCC.4. High-frequency of multiple primary cancers was demonstrated in 23 patients with MSI-H positive from 13 families met the Amsterdam criteria. The subset of patients, with better prognosis. In 18 families of group suspected HNPCC have not found multiple primary cancers. Majority of patients, with poor prognosis. This indicate the patients need test the MSI, It is helpful to Early detection high-risk group of HNPCC, special attention should be paid to the patients in order to make early precaution and treatment, reduce the morbidity and mortality.