Expression of cyclooxygenase-2 and peroxisome proliferator-activated receptor gamma during malignant melanoma progression

Background: Cancer chemoprevention using nonsteroidal anti-inflammatory drugs is frequently attributed to cyclooxygenase-2 (COX-2) inhibition, although recent studies suggest that peroxisome proliferator-activated receptor gamma (PPARγ) may also be involved. While surgical excision remains the treatment mainstay for localized malignant melanoma, certain high-risk patients may benefit from adjunctive chemotherapy. In this study, we compared COX-2 and PPARγ immunohistological staining in benign nevi, primary melanomas and metastatic melanomas to help predict the effectiveness of compounds targeting these markers. Methods: COX-2 and PPARγ immunohistological staining was performed and reviewed in 99 melanocytic lesions, including 38 benign nevi, 32 primary melanomas and 29 metastatic melanomas. Results: There was a significant increase in both COX-2 and PPARγ immunostaining in melanomas compared with benign nevi. Metastatic melanomas were more likely to have a higher number of PPARγ-immunopositive cells. They were also more likely to express COX-2 than primary melanomas. Neither COX-2 nor PPARγ expression was associated with a specific pathologic subtype. Conclusions: COX-2 and PPARγ may help modulate the progression of melanocytic precursor lesions to disseminated malignant melanoma. As such, they may serve as candidate substrates for targeted cancer therapies and may be particularly useful as adjuncts to surgery.