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.
Department of Pathology, UMass Medical School, Worcester, MA, USA.
Vishes
V
Chhibber
Karen
K
Dresser
Meera
M
Mahalingam
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000236:Adenoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020137:Base Pair Mismatch; D014408:Biomarkers, Tumor; D053843:DNA Mismatch Repair; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005820:Genetic Testing; D018095:Germ-Line Mutation; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods*; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000235:genetics / Q000378:metabolism; D009386:Neoplastic Syndromes, Hereditary / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D012626:Sebaceous Gland Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D013577:Syndrome
D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; C094443:G-T mismatch-binding protein; C501486:MLH1 protein, human; D009687:Nuclear Proteins; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein