MSH-6: extending the reliability of immunohistochemistry as a screening tool in Muir-Torre syndrome.

The subtype of Muir-Torre syndrome, allelic to hereditary nonpolyposis colorectal cancer is typically associated with germline mutations in the mismatch repair proteins MSH-2 and/or MLH-1. More recently, mutation in an additional mismatch repair protein MSH-6 has been documented in a patient with Muir-Torre syndrome. Given this, the aim of the present study was to ascertain the frequency of the same in unselected sebaceous gland neoplasms. Overall, we found that 59% of sebaceous neoplasms exhibited a mutation in at least one mismatch repair protein gene -- a prevalence rate similar to that reported previously by others. Of interest, we found MSH-6 to be the mismatch repair protein most commonly lost 17/41 (41%), followed by MSH-2 14/41 (34%) and MLH-18/41 (20%) and the positive predictive value of each were as follows: MLH-1 88%, MSH-6 67% and MSH-2 55%. The frequency of a MSH-6 germline mutation in our cohort indicates that it is not a rare finding. Evidence indicating microsatellite stability in three of 17 patients with a clinical history indicative of Muir-Torre syndrome and a mutation in only MSH-6 suggests that the phenotype of a germline MSH-6 mutation differs from that of MLH-1 and MSH-2 mutations and further supports the use of immunohistochemistry as a screening tool in patients with Muir-Torre syndrome with an extended panel that includes MSH-6.