MSH6 is a DNA mismatch repair protein involved specifically in the mismatch repair of mutations that arise from replication and recombination. Somatic and inherited mutations in this gene lead to microsatellite instability and atypical hereditary nonpolyposis colorectal cancer as well as 10-20% of Lynch Syndrome colorectal cancers. Patients with MSH6 mutations are also at increased risk for endometrial cancer. Genetic testing along with immunohistochemistry staining of this protein is useful for diagnosis and subtyping of colorectal tumors. Staining is nuclear in normal tissues and loss of staining is observed in patients with MMR associated cancers. References: Houlleberghs, 2017; Giglia, 2016; J Natl Cancer inst 2010 102(3):193; Gastroenterol 2004 127(1):17