[Genetic pathways in XXXX : interest for the pathologist].

@entity589 @entity5 @entity984 @entity2536 @entity876 @entity14 @entity1594 @entity2513
Molecular biology studies have led to the identification of two different types of @entity14 . The first group, called LOH (for loss of heterozygosity), represents 80% of @entity14 and is characterised by aneuploidy, allelic losses and a location in the distal colon. The second group displays phenotypic microsatellite instability ( @entity5 ), has a near-diploid karyotype and a relatively low frequency of allelic losses. It accounts for 15% of all @entity14 and for about 30% of right-sided @entity5 . Four different pathways have been identified as responsible for @entity5 progression: the WNT/Wingless, the @entity984 , the Transforming growth factor (TGF) and the @entity876 pathways. The involvement of these pathways depends on the @entity5 type. In @entity5 , the WNT/Wingless pathway is activated through an APC mutation, whereas @entity5 do so through a catenin stabilising mutation. The TGFb growth inhibitory pathway is altered either by mutations in the signal transduction molecules @entity2536 and @entity1594 in LOH positive @entity5 or by mutations of TGFbRII in @entity5 . In the @entity876 pathway, mutations in @entity589 may contribute to the @entity2513 transition just as @entity876 mutations may do in LOH positive @entity5 . Until now, @entity5 phenotype determination has had no clinical implications. However, the predictive value of the MSI status was recently stressed as a predictive factor for response to chemotherapy. Immunohistochemistry could represent a complementary strategy to molecular biology in assessing MSI status. This simple test would allow to screen all @entity14 for MSI status, which would provide valuable management information in addition to the histological assessment for @entity5 stage and grade.
