Abstract:
:In hereditary nonpolyposis colorectal cancer (HNPCC) syndrome, more than 90% of the carcinomas show microsatellite instability (MSI) due to a loss of mismatch repair (MMR) function. Although adenomas are very common in HNPCC and demonstrate an accelerated adenoma-carcinoma sequence, data about the prevalence and development of MSI in these early neoplastic lesions are lacking. To determine whether MSI and loss of MMR-protein expression are already present in early stages of tumorigenesis and could therefore be used as a screening tool to identify HNPCC patients before they develop an invasive carcinoma, we analyzed 71 adenomas of 36 HNPCC patients during a 5-year follow-up study. These 36 patients were part of a cohort of 122 HNPCC patients who were investigated at the Institute of Pathology, Klinikum Kassel, as part of the multicentric German HNPCC Consortium, which currently serves more than 2,880 registered families. The diagnosis of HNPCC was based either on the detection of a pathogenic germline mutation in the MSH2, MLH1, or MSH6 genes or in cases where a pathogenic mutation was not found; diagnosis of HNPCC was made, because all patients fulfilled the Amsterdam or Bethesda criteria and revealed a high degree of MSI (MSI-H) as well as loss of one of the MMR proteins by IHC in the cancer tissue. We found that most adenomas (58/71) were MSI-H and had loss of MMR-protein expression. Of the 71 adenomas, 3 were MSI-H with expression of all MMR proteins, and 3 out of 71 displayed loss of a MMR protein with the microsatellites being classified as microsatellite stable (MSS). However, 7 of the 31 adenomas that were located more than 5 cm away from the carcinoma revealed an MSS status (n=6) or low in MSI (n=1) and expressed all MMR proteins. In summary, a significant percentage of HNPCC-associated adenomas (7/31, 22.6%) developing at a distance of more than 5 cm from the corresponding carcinoma did not show the MSI-H MMR-deficient phenotype and expressed all MMR genes. To our knowledge, this is the first study that shows that in most HNPCC patients, the mutator pathway is already detectable in adenomas, but MMR-proficient adenomas can also be found. Therefore, screening for MMR deficiency should not be applied routinely in adenomas with the goal to identify HNPCC patients.
journal_name
Int J Colorectal Disjournal_title
International journal of colorectal diseaseauthors
German HNPCC Consortium.,Müller A,Beckmann C,Westphal G,Bocker Edmonston T,Friedrichs N,Dietmaier W,Brasch FE,Kloor M,Poremba C,Keller G,Aust DE,Fass J,Büttner R,Becker H,Rüschoff Jdoi
10.1007/s00384-005-0073-6subject
Has Abstractpub_date
2006-10-01 00:00:00pages
632-41issue
7eissn
0179-1958issn
1432-1262journal_volume
21pub_type
杂志文章abstract:BACKGROUND AND AIMS:Anastomotic dehiscence following colorectal surgery is a significant cause of morbidity and mortality. Phenytoin has wound-healing promoting and collagenase inhibitory effects. This study assessed these effects on healing of experimental colonic anastomoses in a rat model. MATERIALS AND METHODS:Nin...
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