Abstract
Lynch syndrome (formerly known as hereditary non-polyposis colorectal cancer) is the most common hereditary colorectal cancer syndrome. The syndrome is caused by a germline mutation of one of the mismatch repair (MMR) genes which are responsible for DNA replication error repair.
Impaired function of the proteins encoded by these genes leads to microsatellite instability (MSI) and forms a suitable background for development and progression of tumours, mainly colorectal cancer. According to recent estimates up to 5% of all cases of colorectal cancer are associated with Lynch syndrome.
Due to this relatively high frequency, familial occurrence, absence of premorbid phenotype and development of malignant tumors in productive age, correct diagnosis is important not only from the ethical but also the economical point of view. Unfortunately, clinical means of diagnostics of Lynch syndrome (like the Amsterdam criteria and Bethesda guidelines) lacks sensitivity.
It was shown that predictive models based on histological signs of MSI are more sensitive than the clinical criteria used to detect patients with suspected Lynch syndrome. Of all MSI-H colorectal cancers, 1/5 is caused by Lynch syndrome, while the rest are sporadic cancers caused by epigenetic inactivation of an MMR gene.
To rule out the sporadic cases, molecular genetic investigation of the BRAF gene and methylation analysis of the MLH1 promoter is used in the diagnostic workup of Lynch syndrome. The suspicion of Lynch syndrome, based on the results of the complex of diagnostic methods mentioned above, should be proved by detection of a germline mutation of an MMR gene in peripheral blood, and followed by screening of family members, which is a necessary condition for efficient prevention.