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The PMS2 post meiotic segregation increased 2 gene is located on chromosome number 7. The gene product of PMS2 forms a heterodimer with MLH1 that interacts with MSH2 bound to mismatched bases in DNA. MSH2 is a protein of 934 aa (100 kDa) localized to the cell nucleus. MSH2 functions as one of the four major DNA mismatch repair genes along with PMS2, MLH1 and PMS1. Mutations in these genes are associated with hereditary nonpolyposis colon cancer (HNPCC), one of the most common hereditary diseases in man. Immunohistochemistry studies have further determined that the microsatellite instability phenotype in endometrial carcinoma is linked to defects in the MLH1/PMS2 gene. Patients with colorectal carcinoma that is mismatch-repair-deficient and confirmed with immunohistochemistry (IHC) (MSH2/MSH6 negative or MLH1/PMS2 deleted) have shown objective response to PD-1 antibody, pembrolizumab (6). PD-L1 IHC test has been demonstrated to be a useful predictive marker for anti-PD-1 immunotherapy in colorectal carcinoma (7).
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1. Cohn DE., Pavelka JC., Frankel WL., Morrison CD., Hampel H., Copeland., LJ., Fowler JM. Correlation between patient weight and defects in DNA mismatch repair: is this the link between an increased risk of previous cancer in thinner women with endometrial cancer? Int J Gynecol Cancer. 2008 Jan-Feb;18(1):136-40.
2. Modica I., Soslow., Black D., Tornos C., Kauff N., Shia J. Utility of immunohistochemistry in predicting microsatellite instability in endometrial carcinoma. Am J Surg Pathol. 2007 May;31(5):744-51.
3. Sordet C., Goetz J., Sibilia. Contribution of autoantibodies to the diagnosis and nosology of inflammatory muscle disease. Joint Bone Spine. 2006 Dec;73(6):646-54.
4. Balogh., Heulings RC., Russo. The mismatch repair gene hPMS2 is mutated in primary breast cancer. Int J Mol Med. 2006 Nov;18(5):853-7.
5. Halvarsson B., Lindblom A., Rambech E., Lagerstedt K., Nilbert M. The added value of PMS2 immunostaining in the diagnosis of hereditary nonpolyposis colorectal cancer. Fam Cancer. 2006;5(4):353-8. Epub 2006 Jul 12.
6. Center for Disease Control Manual. Guide: Safety Management, NO. CDC-22, Atlanta, GA. April 30, 1976 “Decontamination of Laboratory Sink Drains to Remove Azide Salts.”
7. National Committee for Clinical Laboratory Standards (NCCLS). Protection of laboratory workers from infectious diseases transmitted by blood and tissue; proposed guideline. Villanova, PA 1991;7(9). Order code M29-P.