Problematik der Untersuchung von kolorektalen Adenomen für die Erkennung von HNPCC

Abstract

Hereditary non-polyposis colorectal cancer (HNPCC) accounts for approximately 2% of the total colorectal cancer burden and is the most common form of familial colorectal cancer. Diagnosis is confirmed by the detection of a germline mutation in a DNA mismatch repair gene. The use of well-defined microsatellite markers has established diagnostic microsatellite instability (MSI) analysis as a valuable tool. Tumors from HNPCC patients invariably display MSI. Immunohistochemical analysis can specify the mutated gene.

The role of the microsatellite instability in adenomas as the pre-malignant lesion has yet not been elucidated. As a potential source for the broad range of results in MSI testing in adenomas the significance of intralesional heterogeneity has to be determined. Therefore, the aim of the study was to demonstrate problems and pitfalls of the MSI analysis in HNPCC ademomas. In summary 15 syn- or metachronous adenomas from proven HNPCC-patients have been evaluated. The MSI data were correlated to their immunhistochemical data. In 5/15 the precise MSI-result (MSI-H) could be observed only after laser microdissection, which allows the selective examination of adenomatous cells, compared to the crude manual microdissection recommended today. 3/15 adenomas revealed a MSS-status and a regular expression of the mismatch-repair proteins, so that these adenomas had to be classified as sporadic, although one patient had an additional ademoma, which was classified as MSI-H and revealed a loss of protein expression. To our knowledge this is the first study which shows, that the intralesional heterogenity in adenomas of HNPCC may lead to false negative MSI testing and, more important, that sporadic adenomas occur next to HNPCC-associated adenomas in HNPCC-patients.