Mismatch repair proteins expression and microsatellite instability in skin lesions with sebaceous differentiation: a study in different clinical subgroups with and without extracutaneous cancer

Am J Dermatopathol. 2007 Aug;29(4):351-8. doi: 10.1097/DAD.0b013e318057713c.


Muir-Torre syndrome (MTS) is defined as the association of a sebaceous tumor or keratoacanthoma and an extracutaneous neoplasm, mainly from the gastrointestinal or genitourinary tracts. MTS is related to hereditary non-polyposis colorectal cancer (HNPCC), a syndrome with germline mutations in the mismatch repair (MMR) gene(s), leading to microsatellite instability (MSI). In this study, using immunohistochemistry and a microsatellite instability assay, we analyzed the incidence of MMR gene abnormalities in 79 sebaceous lesions from 70 patients, 26 of whom also had an extracutaneous visceral neoplasm. We were unable to investigate the family histories of our patients regarding other tumors in order to assess which of our cases met the Amsterdam criteria. Defective MMR protein expression (MMR-) was found in 18/70 (25.7%) patients, with an identical distribution between those having an isolated skin tumor (11/44, 25.0%) and those with an extracutaneous cancer (7/26, 25.4%). In the sporadic group, MMR negative lesions were significantly more frequent in extrafacial areas (P = 0.03). High concordance was found between MMR expression in sebaceous lesions and the extracutaneous neoplasm in the same patient (20/23, 86.9%), as well as between MMR expression and microsatellite status (18/20, 90%). In conclusion, this study confirms the value of immunohistochemistry to identify MMR defective tumors. However, since only a minority of sebaceous neoplasms in patients who also have an extracutaneous cancer display MMR defects, these techniques are of limited value for the identification of "clinically defined" MTS.

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Base Pair Mismatch*
  • Child
  • DNA Mismatch Repair*
  • DNA Repair Enzymes / genetics*
  • Facial Neoplasms / genetics
  • Facial Neoplasms / pathology
  • Female
  • Gastrointestinal Neoplasms / genetics
  • Gastrointestinal Neoplasms / pathology
  • Germ-Line Mutation / genetics
  • Humans
  • Immunohistochemistry
  • Keratoacanthoma / genetics
  • Male
  • Microsatellite Instability*
  • Middle Aged
  • MutL Protein Homolog 1
  • MutS Homolog 2 Protein / genetics*
  • Neoplasms, Multiple Primary / genetics*
  • Nuclear Proteins / genetics*
  • Sebaceous Gland Neoplasms / genetics*
  • Sebaceous Gland Neoplasms / pathology
  • Syndrome
  • Urinary Bladder Neoplasms / genetics
  • Urinary Bladder Neoplasms / pathology


  • Adaptor Proteins, Signal Transducing
  • MLH1 protein, human
  • Nuclear Proteins
  • MSH2 protein, human
  • MutL Protein Homolog 1
  • MutS Homolog 2 Protein
  • DNA Repair Enzymes