Instabilité microsatellitaire dans le cancer colorectal

Abstract

Microsatellite instability is the molecular fingerprint of a deficient mismatch repair system. This alteration occurs in 15% of colorectal cancers, with two-third being linked to a sporadic disease, and one-third to an inheritance syndrome, the Lynch syndrome. This status, which can be assessed by molecular biology and immunohistochemistry, now belongs to the usual tests performed by the pathologist involved in digestive pathology. MSI determination is a screening method to detect patients who are prone to be affected by Lynch syndrome. Indeed, MSI is present in nearly all patients having Lynch syndrome. In this setting, immunohistochemistry may be helpful in selecting the gene harboring the germline mutation for which the encoded protein is not expressed. The distinction between sporadic and inherited MSI cases can be based on BRAF and hMLH1 hypermethylation. These alterations have never been encountered in Lynch syndrome. In addition, MSI identification in stage II colorectal carcinoma does not favor 5-FU chemotherapy, because this treatment has been shown to negatively impact on overall survival. In order to be optimal, molecular and immunohistochemistry techniques have to be performed in an environment in connection with quality insurance programs.