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 (PPARgamma) 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 PPARgamma immunohistological staining in benign nevi, primary melanomas and metastatic melanomas to help predict the effectiveness of compounds targeting these markers.


METHODS
COX-2 and PPARgamma 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 PPARgamma immunostaining in melanomas compared with benign nevi. Metastatic melanomas were more likely to have a higher number of PPARgamma-immunopositive cells. They were also more likely to express COX-2 than primary melanomas. Neither COX-2 nor PPARgamma expression was associated with a specific pathologic subtype.


CONCLUSIONS
COX-2 and PPARgamma 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.
Lee
Carolyn
C
Department of Dermatology, Stanford University School of Medicine, Stanford, CA 94305, USA. carilee@stanford.edu
Ramirez
James A
JA
Guitart
Joan
J
Diaz
Leslie K
LK
D014408:Biomarkers, Tumor / Q000378:metabolism; D002452:Cell Count; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D018450:Disease Progression; D006801:Humans; D007150:Immunohistochemistry; D008545:Melanoma / Q000378:metabolism* / Q000556:secondary; D047495:PPAR gamma / Q000378:metabolism*; D012878:Skin Neoplasms / Q000378:metabolism* / Q000473:pathology
D014408:Biomarkers, Tumor; D047495:PPAR gamma; D051546:Cyclooxygenase 2