PMS2 [MD101R]

PMS2, a mismatch repair endonuclease, is a member of a family of genes involved in DNA mismatch repair. Carriers of the mismatch repair gene mutations have a high lifetime risk of developing Hereditary Non-Polyposis Colon Cancer (HNPCC) and several other cancers including endometrial cancer due to microsatellite instability (MSI) caused by accumulation of DNA replication errors in proliferating cells. Along with MLH1, MSH2 and MSH6, PMS2 antibody is helpful in diagnosis of MSI. An IHC study conducted by Mayo Clinic on 535 cases with MSI-high, 90% of the tumors showed loss of MLH1, MSH2 and/or MSH6 expression, while 70% of the remaining cases showed isolated loss of PMS2 expression. The loss of PMS2 was associated with young age of diagnosis and right-sided location, but not with a striking family history of cancer. Endometrial carcinomas are the most common non-colorectal cancers associated with Lynch syndrome. The most common IHC abnormality in endometrial carcinomas with MSI was concurrent loss of MLH1/PMS2. Adding PMS2 and MSH6 to MLH1 and MSH2 antibodies increased sensitivity for diagnosis of MSI. Tumors with low-level MSI show unfavorable pathological characteristics compared to tumors with no MSI and tumors with high-level MSI.