Microsatellite instability testing and its role in the management of XXXX .

@entity1 @entity6756 @entity124 @entity4309 @entity5 @entity4311 @entity14437 @entity1487 @entity14 @entity4638
OPINION STATEMENT: TNM stage remains the key determinant of @entity1 prognosis after surgical resection of @entity14 ( @entity14 ), and informs treatment decisions. However, there is considerable stage-independent variability in clinical outcome that is likely due to molecular heterogeneity. This variability underscores the need for robust prognostic and predictive biomarkers to guide therapeutic decision-making including the use of adjuvant chemotherapy. Although the majority of CRCs develop via a chromosomal instability pathway, approximately 12-15  % have deficient DNA mismatch repair (dMMR) which is characterized in the @entity5 by @entity124 ( @entity124 ). Tumors with the dMMR/ @entity124 develop from a germline mutation in an MMR gene ( @entity6756 , @entity4311 , @entity4638 , @entity14437 ), i.e., @entity4309 , or more commonly from epigenetic inactivation of @entity6756 MMR gene. CRCs with dMMR/ @entity124 status have a distinct phenotype that includes predilection for the proximal colon, poor differentiation, and abundant @entity5 -infiltrating lymphocytes. Consistent data indicate that these @entity5 have a better stage-adjusted survival compared to proficient MMR or microsatellite stable (MSS) @entity5 and may respond differently to @entity1487 -based adjuvant chemotherapy. To increase the identification of dMMR/ @entity124 @entity1 in clinical practice that includes those with @entity4309 , it is recommended that all resected CRCs to be analyzed for MMR status. Available data indicate that @entity1 with stage II dMMR CRCs have an excellent prognosis and do not benefit from @entity1487 (FU)-based adjuvant chemotherapy which supports their recommended management by surgery alone. In contrast, the benefit of standard adjuvant chemotherapy with the FOLFOX regiment in stage III dMMR @entity14 @entity1 awaits further study and therefore, all @entity1 should be treated with standard adjuvant FOLFOX.
