Peroxisome proliferator-activated receptors in squamous cell carcinoma and its precursors.
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.
Nijsten
Tamar
T
Department of Dermatology, University Hospital Antwerp, Antwerp, Belgium. tamar.nijsten@uza.be
Geluyckens
Elke
E
Colpaert
Cecile
C
Lambert
Julien
J
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
D008565:Membrane Proteins; D047493:PPAR alpha; D047495:PPAR gamma; D048068:PPAR-beta; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases