Review article: Detection and management of hereditary non-polyposis colorectal cancer (Lynch syndrome).
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.


OBJECTIVE
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.
Ramsoekh
D
D
Department of Gastroenterology & Hepatology, Erasmus MC University Medical Center, Rotterdam, The Netherlands. d.ramsoekh@erasmusmc.nl
Van Leerdam
M E
ME
Wagner
A
A
Kuipers
E J
EJ
D011125:Adenomatous Polyposis Coli / Q000235:genetics*; D017668:Age of Onset; D020137:Base Pair Mismatch / Q000235:genetics*; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000175:diagnosis* / Q000235:genetics / Q000628:therapy; D004252:DNA Mutational Analysis / Q000379:methods; D020022:Genetic Predisposition to Disease; D006801:Humans; D053842:Microsatellite Instability; D012307:Risk Factors