open access: 2012 - Clinicopathological Features and Management of Cancers in Lynch Syndrome

Clinicopathological Features and Management of Cancers in Lynch Syndrome

Abstract

Lynch syndrome (LS) is characterized by an autosomal dominant inheritance of the early onset of colorectal cancer (CRC) and endometrial cancer, as well as increased risk for several other cancers including gastric, urinary tract, ovarian, small bowel, biliary tract, and brain tumors. The syndrome is due to a mutation in one of the four DNA mismatch repair (MMR) genes MLH1, MSH2, MSH6, or PMS2. The majority of LS patients and families can now be identified, and the underlying mutation detected using genetic diagnostics. Regular surveillance for CRC and endometrial cancer has proved beneficial for mutation carriers. However, screening for other tumors is also recommended even though experiences in the screening of these tumors is limited. Prophylactic colectomy, prophylactic hysterectomy, and bilateral salpingo-oophorectomy may be reasonable options for selected patients with LS. This paper describes the features and management of LS.

1. Introduction
Lynch syndrome (LS), also referred to as hereditary non-polyposis colorectal cancer (HNPCC), is the most common form of hereditary colorectal cancer, accounting for 2–5% of all colorectal cancer (CRC) cases [1, 2]. The cancer predisposition in LS arises from germline mutations in any of the four DNA mismatch repair (MMR) genes MLH1, MSH2, MSH6, or PMS2 [3]. The mutation carriers are at high risk for developing CRC and endometrial cancer at a young age [4]. Many other tumor types such as gastric, ovarian, small bowel, urinary, and biliary tract, as well as brain tumors, have also been associated with LS [5, 6]........

10. Conclusions
Knowledge of the tumor spectrum in Lynch syndrome is important in planning strategies for the management of patients with this syndrome. Screening proved beneficial only for CRC and endometrial cancer although screening for other tumors is also recommended. Family history is an important tool for identifying LS. Clinical criteria serve to select suspected cases for molecular studies, such as MSI analysis of the tumors or immunohistochemical analysis of the MMR proteins. It is now possible to undertake predictive genetic testing in family members once a mutation has been detected in a family. However, it is important to organize genetic counselling individually before genetic testing. Genetic testing allows clinical screening to target mutation carriers while excluding mutation-negative individuals from further examination.