Table 3.

Probability of identifying a germline Lynch Syndrome mutation based on microsatellite instability testing or immunohistochemistry result.^14,17,23,32

Mircosatellite Instability/Immunohistochemistry Result	Probability of identifying a germline mutation	Advantages	Disadvantages
MSI-High	21%	MSI-high when mutations results in expression of non-functional mismatch repair protein MSI-High when mismatch repair proteins other than MLH1/MSH2/MSH6/PMS2 are mutated	Requires more tissue and a source of normal Requires tissue microdissection prior to PCR Decreased sensitivity in tissues outside the colon MSI-L in endometrial cancer is of uncertain significance Mutations in MSH6 are more often associated with MSI-L or MSS
Any type of IHC loss	21%	Lower cost Loss of protein expression points to specific gene affected Technique is more widely available Requires less tissue	Mutations resulting in expression of non-functional proteins result in intact IHC Expression of some proteins, especially MSH6, can be focal Requires individual pathologist interpretation Loss of MLH1 requires subsequent PCR-based MLH1 promoter methylation analysis
IHC loss of MLH1/PMS2 (and absence of MLH1 promoter methylation)	33%
IHC loss of MSH2/MSH6	67%
IHC loss of MSH6	24%
IHC loss of PMS2	62%