Abstrakt
Lynch syndrome (LS) is an autosomal dominant inherited syndrome, with predisposition to multiple cancer types. It is the most common cause of familial colorectal cancer (CRC) with a known genetic background.
In woman carriers of LS, the risk of endometrial cancer almost equals the risk of CRC. LS is defined by germline mutation in one of the DNA mismatch repair protein (MMRP) genes, which are responsible for corrections of errors occuring during DNA replication.
Marker of MMRP deficiency is microsatellite instability (MSI), occuring also in a proportion of sporadic CRCs. Revised Bethesda Guidelines (RBG), the most commonly used clinical criteria for LS detection, have relatively low sensitivity and specificity.
It is estimated that RBG fail to identify 20-30 % cases of LS associated CRCs. Role of the pathologist is to increase detection of LS.
For that purpose, complex algorithm is used, based on histomorphology (detection of MSI-high histology in CRC), immunohistochemistry (expression of MMRP and other proteins) and molecular pathology. First objective is to detect MSI-high CRC, and differentiate between sporadic and LS associated tumors.
Finaly, diagnosis of LS is confirmed by germline mutation testing, guided by the immunohistochemistry of MMRP.