Frequency of microsatellite instability in unselected sebaceous gland neoplasias and hyperplasias

J Invest Dermatol. 2003 May;120(5):858-64. doi: 10.1046/j.1523-1747.2003.12125.x.


Sebaceous gland neoplasias are the cutaneous manifestation of the Muir-Torre syndrome, which is known to be a phenotypical variant of hereditary nonpolyposis colorectal cancer. Both hereditary nonpolyposis colorectal cancer and Muir-Torre syndrome are caused by inherited DNA mismatch repair defects. As a prominent molecular genetic feature, all tumors associated with a DNA mismatch repair defect exhibit high microsatellite instability. So far, the frequency of DNA mismatch repair defects in patients selected solely on the basis of a sebaceous gland tumor has never been determined. In order to estimate this frequency, we assessed microsatellite instability with up to 10 microsatellite markers in a newly collected unselected series of 25 sebaceous gland neoplasias (six sebaceous adenomas, 16 sebaceous epitheliomas, three sebaceous carcinomas) in comparison to 32 sebaceous gland hyperplasias from unrelated patients. As many as 15 of the 25 sebaceous gland neoplasias (60%), but only one of the 32 sebaceous gland hyperplasias (3%), exhibited high microsatellite instability. Thus, in our study, the majority of patients with a sebaceous gland neoplasia in contrast to patients with a sebaceous gland hyperplasia are highly suspicious for an inherited DNA mismatch repair defect. On the basis of the subsequently collected tumor histories, nine of the 15 patients with a high microsatellite unstable sebaceous gland neoplasia were identified to have Muir-Torre syndrome. In none of these cases, however, were the clinical Amsterdam criteria for diagnosing hereditary nonpolyposis colorectal cancer fulfilled. In the sebaceous tumors of the remaining six patients, high microsatellite instability was an incidental finding. In two of these six patients, single relatives were known to be affected with internal cancer; however, their family histories were not suggestive of Muir-Torre syndrome or hereditary nonpolyposis colorectal cancer. In comparison with microsatellite instability screening studies in a variety of other randomly selected tumors, our study identifies sebaceous gland neoplasias as tumors with the highest frequency of high microsatellite instability reported so far, whereas sebaceous gland hyperplasia rarely exhibits high microsatellite instability. Therefore, screening for microsatellite instability in sebaceous gland neoplasias will be of great value in the detection of an inherited DNA mismatch repair defect, which predisposes to various types of internal cancers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Base Pair Mismatch
  • Biomarkers, Tumor
  • Colorectal Neoplasms / metabolism
  • DNA Repair
  • Female
  • Fibroblasts / metabolism*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Hyperplasia / metabolism
  • Hyperplasia / pathology*
  • Male
  • Microsatellite Repeats*
  • Middle Aged
  • Phenotype
  • Risk Factors
  • Sebaceous Gland Neoplasms / genetics*
  • Sebaceous Gland Neoplasms / metabolism*
  • Skin Neoplasms / genetics*
  • Skin Neoplasms / metabolism*


  • Biomarkers, Tumor