Current definition requires evidence of dysfunctional germ line mutations in DNA mismatch repair enzymes
We prefer to evaluate both PCR based microsatellite repair instability (MSI) / stability (MSS) and intact / absent immunohistochemical expression of DNA mismatch repair enzymes
Genetic counseling should be offered before genetic or immunohistologic testing is performed
PCR test evaluates 5 microsatellites in neoplastic vs. normal tissue
If ≥2 are altered, designate as MSI-high (MSI-H)
If one is altered, designate as MSI-low (MSI-L)
If none altered, designate as MSS
If more than 5 microsatellites evaluated, alter criteria proportionally
Immunohistochemical test evaluates presence of mismatch repair enzymes
It does not evaluate presence of functional enzyme
Miss-sense mutations may result in an immunohistochemically positive result but a non-functional enzyme
Most commonly evaluated enzymes are MLH1, MSH2 and PMS2 and may include MSH6
PMS2 requires MLH1 expression, thus may be absent if MLH1 is lost
MSH6 requires MSH2 expression, thus may be absent if MSH2 is lost
Clear absence of an enzyme is abnormal
Immunohistologic and Genetic Differences between Familial and Sporadic Cases
