title: MSH-2 and MLH-1 protein expression in Muir Torre syndrome-related and sporadic sebaceous neoplasms.
abstract: BACKGROUND
  Muir-Torre Syndrome (MTS) is a rare autosomal-dominant disorder characterized by the predisposition to both sebaceous neoplasm and internal malignancies. MTS-associated sebaceous neoplasms reveal mutations in DNA mismatch repair (MMR) genes and microsatellite instability. A significant part of MTS patients represents a phenotypic variant, the hereditary nonpolyposis colorectal cancer (HNPCC). A strong correlation between microsatellite instability and immunostaining has been demonstrated. The early recognition of sebaceous neoplasm as part of MTS, and their differentiation from sporadic sebaceous neoplasm may have an important application in a clinical setting. The absence of MLH-1 or MSH-2 expression by immunostaining identifies tumors with mismatch repair deficiency.
  
  
  OBJECTIVE
  Our aim is to determine whether an immunohistochemical approach, targeting DNA repair proteins MSH-2 and MLH-1 in MTS-related sebaceous neoplasm and their sporadic counterparts, can be used for their identification.
  
  
  METHODS
  We examined 15 sebaceous neoplasms (including 6 internal malignancy- associated sebaceous neoplasms and 8 sporadic sebaceous neoplasms) from 11 patients for the expression of MSH-2 and MLH-1 by immunohistochemistry.
  
  
  RESULTS
  Four of 5 internal malignancy-associated sebaceous neoplasms showed loss of expression of MSH-2 or MLH-1. Correlation of the immunostaining pattern of the sebaceous neoplasms and the patients' positive history of colon carcinoma was 80%. Seven of 8 sporadic sebaceous neoplasms showed a positive expression of MSH-2 and MLH-1. The prevalence for loss of expression of MMR proteins in sebaceous neoplasms was 38.5%. MMR immunostaining had 87.5% specificity and 80% sensitivity.
  
  
  CONCLUSIONS
  This study is limited by a small sample size, and by bias selection due to the use of non nationwide data-base as the resource of cases.
  
  
  CONCLUSIONS
  Our findings demonstrate that immunohistochemical testing for internal malignancy-associated sebaceous neoplasms is a practical approach to confirm a suspected inherited MMR gene defect, and an accurate method to distinguish between sporadic and MTS-associated sebaceous lesions.
authors.affiliation: Department of Dermatology, School of Medicine, University of Puerto Rico, San Juan, PR. amorales@rcm.upr.edu
authors.forename: Adisbeth
authors.initials: A
authors.lastname: Morales-Burgos
authors.forename: Jorge L
authors.initials: JL
authors.lastname: Sánchez
authors.forename: Luz D
authors.initials: LD
authors.lastname: Figueroa
authors.forename: Wilfredo E
authors.initials: WE
authors.lastname: De Jesús-Monge
authors.forename: Marcia R
authors.initials: MR
authors.lastname: Cruz-Correa
authors.forename: Carmen
authors.initials: C
authors.lastname: González-Keelan
authors.forename: Cruz María
authors.initials: CM
authors.lastname: Nazario
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000096:biosynthesis*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D055653:Muir-Torre Syndrome / Q000378:metabolism*; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000096:biosynthesis*; D009687:Nuclear Proteins / Q000096:biosynthesis*; D012626:Sebaceous Gland Neoplasms / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C501486:MLH1 protein, human; D009687:Nuclear Proteins; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein