title: Sebaceous neoplasms and the immunoprofile of mismatch-repair proteins as a screening target for syndromic cases.
abstract: BACKGROUND
  Muir-Torre syndrome (MTS), a subset of Lynch syndrome, is characterized by concurrent or sequential development of sebaceous neoplasms, and internal malignancies, specifically colorectal carcinoma (CRC), and can be related to mismatch-repair (MMR)-protein deficiency. In CRC context, p16-negativity in MLH1-deficient cases may denote methylation rather than mutation. The prime aim of this study was to evaluate the mismatch-repair (MMR)-protein deficiency and the p16 status among sebaceous neoplasms.
  
  
  METHODS
  From January 1990 through October 2012, 26 sebaceous adenomas (SAs) and 6 sebaceous carcinomas (SCs) were accrued. The expression of MLH1, MSH2, MSH6, and PMS2 was recorded. MLH1-deficient cases were tested for p16 status.
  
  
  RESULTS
  Eighteen (56%) of the 32 specimens with SA or SC displayed MMR-protein deficiency, comprising 17 (65.4%) SAs (MSH2/MSH6 loss in 12, MLH1/PMS2 loss in 3, MSH6 loss only in 2 cases) and 1 (16.7%) SC (MLH1/PMS2 loss). All 4 MLH1 deficient cases were p16-positive.
  
  
  CONCLUSIONS
  A substantial proportion of sebaceous neoplasms were MMR-protein deficient and thus likely MTS candidates. Given the low prevalence of sebaceous neoplasms in Denmark, immunohistochemistry for the four MMR-proteins is recommended in the initial diagnostic approach. The addition of p16 was none-informative, but evaluation of its utility in larger series is warranted.
authors.affiliation: Department of Pathology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. Electronic address: marieboennelycke@gmail.com.
authors.forename: Marie
authors.initials: M
authors.lastname: Boennelycke
authors.affiliation: Department of Pathology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Birthe M
authors.initials: BM
authors.lastname: Thomsen
authors.affiliation: Department of Pathology, Copenhagen University Hospital Hvidovre, Denmark.
authors.forename: Susanne
authors.initials: S
authors.lastname: Holck
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism*; D053843:DNA Mismatch Repair / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D009154:Mutation / Q000235:genetics; D012626:Sebaceous Gland Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing
keywords: Mismatch-repair proteins; Muir–Torre syndrome; Sebaceous adenoma; Sebaceous carcinoma; p16