title: Peroxisome proliferator-activated receptors in squamous cell carcinoma and its precursors.
abstract: BACKGROUND
  Peroxisome proliferator-activated receptors (PPARs) mediate several functions that are of interest in carcinogenesis. Although PPARalpha, PPARbeta, and PPARgamma are expressed in multiple human, their expression has not been investigated in non-melanoma skin cancer.
  
  
  METHODS
  We performed a retrospective paired immunohistochemical analysis of normal skin, actinic keratosis (AK), and squamous cell carcinoma (SCC) among 35 individuals. Specimens were considered PPAR immunoreactive when 1% or more of the tumor cells showed clear evidence of immunostaining. Cyclooxygenase-2 (COX-2) expression, the fraction of proliferating endothelial cells, and microvessel density were also evaluated in these samples.
  
  
  RESULTS
  PPARalpha immunoreactivity was significantly less likely to occur in SCC and AK than in normal skin of each individual. In contrast to PPARalpha, PPARbeta appeared to be upregulated in (pre)malignant skin lesions. For each individual, the likelihood that normal skin, AK, or SCC was immunoreactive against PPARgamma was comparable. COX-2 immunopositivity was significantly associated with PPARbeta and PPARgamma immunoreactivity. No statistical differences were noted for the angiogenesis parameters and PPARalpha, PPARbeta, or PPARgamma expression, except that the microvessel density was significantly higher among PPARbeta-immunoreactive SCCs compared to that among immunonegative SCCs.
  
  
  CONCLUSIONS
  Although further research is warranted, these results suggest that PPAR ligands such as fibrates and thiazolidinediones may have chemoprophylactic properties in skin carcinogenesis.
authors.affiliation: Department of Dermatology, University Hospital Antwerp, Antwerp, Belgium. tamar.nijsten@uza.be
authors.forename: Tamar
authors.initials: T
authors.lastname: Nijsten
authors.forename: Elke
authors.initials: E
authors.lastname: Geluyckens
authors.forename: Cecile
authors.initials: C
authors.lastname: Colpaert
authors.forename: Julien
authors.initials: J
authors.lastname: Lambert
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000098:blood supply / Q000378:metabolism*; D016022:Case-Control Studies; D051546:Cyclooxygenase 2; D006801:Humans; D007150:Immunohistochemistry; D007642:Keratosis / Q000378:metabolism; D008565:Membrane Proteins; D009389:Neovascularization, Pathologic / Q000378:metabolism; D047493:PPAR alpha / Q000378:metabolism*; D047495:PPAR gamma / Q000378:metabolism*; D048068:PPAR-beta / Q000378:metabolism*; D011230:Precancerous Conditions / Q000098:blood supply / Q000378:metabolism*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D015203:Reproducibility of Results; D012189:Retrospective Studies; D012878:Skin Neoplasms / Q000098:blood supply / Q000378:metabolism*; D014018:Tissue Distribution
chemical_list: D008565:Membrane Proteins; D047493:PPAR alpha; D047495:PPAR gamma; D048068:PPAR-beta; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases