Das Lynch-Syndrom – Epidemiologie, Klinik, Genetik, Screening, Therapie

Abstract

Lynch syndrome is characterised by a familial predisposition of colorectal and endometrial carcinomas in association with a variety of other cancers. The underlying autosomal dominant inheritance has a penetrance of 85-90%. The molecular genetic underlying mechanism is a mutation in one of the mismatch-repair genes. The identification of the molecular genetic basis of Lynch syndrome enabled the implementation of predictive testing in families with a proven mutation. A prerequisite to detect patients with Lynch syndrome is a knowledge of the clinical and histopathological features of this disease. Typical for Lynch syndrome associated carcinomas is the early age of onset of about 45 years as well as the characteristic localisation within the right hemicolon. However, in order to increase the rate of identification of this underestimated syndrome, the awareness of the clinician must extend beyond this classical phenotype. For this purpose close interdisciplinary cooperation is warranted! The cancers are mostly low-differentiated with solid areas without a tubular structure. Crohn's-like lesions as well as peritumoural and tumour-infiltrating lymphocytes may frequently be found in the periphery of the malignant formation. Within the framework of the clinical evaluation of any index patient, an extended family history must be ascertained and matched with the Amsterdam-I and -II criteria as well as with the revised Bethesda criteria. If a patient fulfills these criteria, testing for microsatellite instability and if positive after genetic counselling mutation analysis should be recommended. Patients with a proven mutation and high risk individuals from families with an unidentified underlying mutation are encouraged to participate in an intensified screening programme. Due to the incomplete penetrance there is no recommendation towards prophylactic surgery in high-risk individuals without tumour manifestation. Nevertheless, the effect on quality of life of prophylactic, extended surgery in addition to the obligatory oncologic resection with or without prophylactic hysterectomy needs to be established in prospective controlled trials.