|
|
Diagnosis of Lynch syndrome based on pathologic examination
KRAUSOVÁ, Lenka
Lynch syndrome is an autosomal dominant disease predisposing to cancer development. Up to 5 % of colorectal cancers may be associated with Lynch syndrome. Due to its familial occurrence the diagnosis is important for family screening. Currently it is based on methods of modern pathology. Theoretical part describes structure of gastrointestinal tract, definition and history of Lynch syndrome, and methods of its laboratory diagnostics. The diagnosis can be based on evaluation of tumor microscopical features (Semi PREDICT score) in tissue sections, imunohistochemical investigation of MMR (mismatch repair) proteins, or molecular genetic MSI (microsatellite instability) testing. Practical part focuses mainly on correlation of immunohistochemistry and MSI testing. Randomly selected cases of colorectal cancer were organized into 2 study groups. The first group consisted of 25 cases with intact MMR immunoexpression, the second group comprised 25 cases with at least one MMR protein being deficient. For further verification molecular genetic MSI testing, along with BRAF gene analysis and MLH1 promoter methylation status to discriminate Lynch syndrome from sporadic cases, were performed. Germline analysis of MMR genes proved the diagnosis of Lynch syndrome in 5 cases of the second group. Semi PREDICT score sensitivity for MMR-deficiency prediction (and indirectly for Lynch syndrome detection) was 84 %, specificity 48 %. Sensitivity of MSI testing was 87 %, but only 50 % in Lynch syndrome subset of cases, specificity was 100 %. The results show major role of MMR immunohistochemistry in the diagnostics of MSI-H cancers, which is the cornerstone of Lynch syndrome screening.
|
guest ::
