Study Of Detection Strategy For Sporadic Colorectal Carcinoma With The Mutator Phenotype

Object: 1.To investigate the changes of clinical and pathological parameters with colorectal cancer in PLA General Hospital in last decade; 2. To investigate clinicopathologic characteristics and early diagnosis of hereditary colorectal cancer; 3. To assess the feasibility of using clinical informations, pathological features, immunohistochemistry and microsatellite analysis to identify patients with the mutator phenotype.Methods: 1. The first part: Retrospective analysis of colorectal cancer(CRC) in Department of General Surgery of PLA General Hospital between Jan 1st 1993 and Jun 30th 2003. Patients were divided into two 5-year-and-3-month cohorts (cohort 1, Jan 1st 1993-Mar 31th 1998; cohort 2 , Apr 1st 1998- Jun 30th 2003).We record demographic data, age, gender, anatomical subsite distribution, histological type, grade and tumor stage; 2.The second part: Retrospective analysis of colorectal cancer(CRC) in Department of General Surgery of PLA General Hospital between Jan 1 st 1993 and Jun 30th 2003. By harvesting cues from the family history of probands with hereditary colorectal cancer, the pedigrees and all lineal and collateral relatives were investigated.The every pedigree tree was protracted. Analyzed ten consecutive pedigrees and summed up the clinicopathologic characteristics; 3.The third part: 232 colorectal carcinomas were grouped according to easily identifiable phenotype and analysed for microsatellite instability (at least two markers affected) and expression of hMLH1 and hMSH2.Results: 1.The first part: A total of 2379 consecutive patients with mean age of 56.8 were recorded. Nine hundred and six-eight patients withmean age of 55.1 years were admitted during the period from Jan 1, 1993 to Mar 31,1998 (first phase) , and other 1411 with a mean age of 56.8 years from Apr 1, 1998 to Jun 30, 2003 (second phase) (PO.OOl).The proportions of proximal colonic cancer and distal colorectal cancer were 21.6% , 78.4% and 26.4% , 73.6% respectively during the first and second phases(p<0.01). The proportions of patients with Dukes'A+B and Dukes'C+D were 39.3% , 60.7% and 49.6%, 50.4% respectively during the first and second phases (PO.001). 2.The second part: A total of 2379 consecutive patients were diagnosed, of whom 6 patients (0.25%) with mean age of 35 were in line with Amsterdam criteria; the ratio of middle and poor to good differentiated adenocarcinoma of 6 probands was 5:1.4 patients (0.17%) with the mean canceration age was 40.25 accorded with criteria of familial adenomatous polyposis ( FAP). Twenty hereditary nonpolyposis colorectal cancer ( HNPCC) patients from 6 unrelated kindreds was observed, mean age at diagnosis was 42.35; the ratio of man to women was 1.22:1; The proportions of proximal (proximal to the spleen flexure) to distal colorectal cancer(distal to the spleen flexure)were 1.5:l;all but 4 patients were alive and well, of whom 1 had been existed for ten years. Forteen FAP patients from 4 unrelated kindreds was found, the ratio of man to women was 1.33:1; mean canceration age was 40.5. 3.The third part: There were 13/39 (33.33%) patients with left colon of early onset group, 10/39 (25.64%) with right colon of early onset group; 11/33 (33.33%) with right colon of late onset group; 9/29 (31.03%) with synchronous and metachronous colorectal carcinoma group; 19/46 (41.03%) with familial carcinoma group showed MSI-H. However, 0/40 patients who developed a solitary carcinoma of the left colon over the age of 50 showed MSI-H. We found a strong concordance between tumors displaying MSI and protein expression of hMLHl or hMSH2 in 216/232 (93.10%) of the cases. Although tumors from 6 patients exhibited MSH-H, the protein expression of MLH1 and MSH2...