Background:  Peroxisome proliferator‐activated receptors (PPARs) mediate several functions that are of interest in carcinogenesis. Although PPARα, PPARβ, and PPARγ 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:  PPARα immunoreactivity was significantly less likely to occur in SCC and AK than in normal skin of each individual. In contrast to PPARα, PPARβ appeared to be upregulated in (pre)malignant skin lesions. For each individual, the likelihood that normal skin, AK, or SCC was immunoreactive against PPARγ was comparable. COX‐2 immunopositivity was significantly associated with PPARβ and PPARγ immunoreactivity. No statistical differences were noted for the angiogenesis parameters and PPARα, PPARβ, or PPARγ expression, except that the microvessel density was significantly higher among PPARβ‐immunoreactive SCCs compared to that among immunonegative SCCs.

Conclusion:  Although further research is warranted, these results suggest that PPAR ligands such as fibrates and thiazolidinediones may have chemoprophylactic properties in skin carcinogenesis.