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

UMMS Affiliation

Department of Pathology

Publication Date


Document Type



Adaptor Proteins, Signal Transducing; Adenoma; Adult; Aged; Aged, 80 and over; Base Pair Mismatch; DNA Mismatch Repair; DNA-Binding Proteins; Female; *Genetic Screening; Germ-Line Mutation; Humans; Immunohistochemistry; Male; Microsatellite Repeats; Middle Aged; MutS Homolog 2 Protein; Neoplastic Syndromes, Hereditary; Nuclear Proteins; Sebaceous Gland Neoplasms; Syndrome; Tumor Markers, Biological


Life Sciences | Medicine and Health Sciences


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.

DOI of Published Version



Mod Pathol. 2008 Feb;21(2):159-64. Epub 2007 Dec 7. Link to article on publisher's site

Journal/Book/Conference Title

Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc

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Link to Article in PubMed

PubMed ID