MMR IHC

MLH1 partners with PMS2 , and MSH2 partners with MSH6.

MLH1 and MSH2 are the dominant partners, so if one of these is lost, it’s partner will be lost too. If the non-dominant partner is lost, the dominant partner will remain.

If PMS2 is lost, the IHC results will be: MLH1 positive, PMS2 negative, MSH2 positive, and MSH6 positive.

If MMR mutations are present, microsatellite DNA (repetitive DNA) will be prone to mutation - this is measured by PCR, with greater than 2 of 5 tested microsatellite mutations being considered MSI-high.

Tumors that are MSI-H / MMR deficient have a better prognosis, are not prone to metastasis, and require less aggressive treatment.

Loss of expression of one of four MMR proteins (tested by IHC) results in microsatellite instability in > 2 of 5 markers (tested by PCR).

MLH1 partners with PMS2, and MSH2 partners with MSH6. MLH1 and MSH2 are the dominant partners, so if one of these is lost, it’s partner will be lost too.