MSI/MMR-deficient tumor diagnosis: Which standard for screening and for diagnosis? Diagnostic modalities for the colon and other sites: Differences between tumors

Microsatellite instability (MSI), which is caused by deficiency of the DNA mismatch repair (MMR) system, is the molecular abnormality observed in tumors associated with Lynch syndrome. Lynch syndrome represents one of the most frequent conditions of cancer predisposition in human, thus requiring specific care and genetic counseling. Moreover, research has recently focused increasingly on MMR deficiency due to its positive predictive value for the efficacy of immune checkpoints inhibitors (ICKi) in metastatic tumors, regardless of their primary origin. MSI has also been demonstrated to constitute an independent prognostic factor in several tumor types, being also associated with alternative response to chemotherapy. These observations have led many professional medical organizations to recommend universal screening of all newly diagnosed colorectal cancers for dMMR/MSI status and increasing evidence support the evaluation of MSI in all human tumors regardless of the cancer tissue of origin. Currently, two standard reference methods, namely immunohistochemistry and polymerase chain reaction, are recommended for the detection of dMMR/MSI status. These methods are equally valid as the initial screening test for dMMR/MSI in colorectal cancer. To date, there is no recommendation for the detection of dMMR/MSI in other primary tumors. In this review, we will present a comprehensive overview of the methods used for evaluation of tumor dMMR/MSI status in colorectal cancer, as well as in other tumor sites. We will see that the evaluation of this status remains challenging in some clinical settings, with the need to improve the above methods in these specific contexts. L’instabilité des microsatellites (MSI), due à la déficience du système MMR (pour mismatch repair), est l’anomalie moléculaire observée dans les tumeurs du syndrome de Lynch. Le syndrome de Lynch représente le plus fréquent des syndromes de prédisposition aux cancers, ce qui nécessite une prise en charge spécifique et un avis du conseil génétique. Par ailleurs, la recherche s’est récemment beaucoup intéressée au statut MSI en raison de sa valeur prédictive quant à l’efficacité des inhibiteurs des immunes checkpoints (ICKi) dans les tumeurs à un stade métastatique, quelle que soit leur origine. Le statut MSI constitue également un facteur pronostique indépendant dans plusieurs types tumoraux, du fait de son association à des réponses alternatives à la chimiothérapie. Ces données ont conduit un grand nomb