Background: The most common hereditary colorectal cancer syndrome is hereditary non-polyposis colorectal cancer (HNPCC), also known as Lynch syndrome. Diagnosis of this syndrome is difficult, because of lack of specific diagnostic features.
Aim: To discuss the diagnostic criteria and laboratory work up for HNPCC. Furthermore, surveillance programs for HNPCC and treatment of HNPCC associated colorectal cancer are discussed.
Results: Current diagnostic criteria, including the Amsterdam II and Bethesda criteria, are suboptimal for the detection of HNPCC. Molecular screening by microsatellite instability (MSI) and immunohistochemistry (IHC) is useful in the diagnosis of HNPCC. Both techniques have a higher sensitivity compared to the Amsterdam II and Bethesda criteria. A combination of both MSI and IHC provides the most optimal selection for mutation analysis. After identification of a mutation in an affected individual, genetic counselling and presymptomatic mutation analysis should be offered to relatives. Furthermore, colonoscopic surveillance should be performed in proven mutation carriers.
Conclusions: Identification of HNPCC is a clinical challenge involving many clinicians. Identification of persons at risk can be achieved by a combination of a detailed family history, testing with molecular and mutation analysis.