Expression of cyclooxygenase-2 (COX-2) and peroxisome proliferator-activated receptor gamma (PPARγ) in skin tumors

AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA 175 Background: To investigate whether protein expression of cyclooxygenase-2 (COX-2) and peroxisome proliferator-activated receptor gamma (PPARγ) is associated with clinico-pathologic characteristics in benign and malignant skin tumors. Methods: Two tissue microarrays (TMAs) were used to analyze COX-2, PPARγ, TP53, and the Ki67 labeling index immunohistochemically. TMA-1 (n=323) consisted of malignant melanomas, nevi, squamous cell carcinomas, basal cell carcinomas, Kaposi sarcomas, histiocytomas, capillary hemangiomas, and sebaceous adenomas. TMA-2 consisted of 88 malignant melanomas with follow-up data, 101 melanoma metastases and 161 benign nevi. Cytoplasmic COX-2 and nuclear PPARγ expression was scored semiquantitatively (0-3+). Results: Using TMA-1, COX-2 and PPARγ expression of any intensity was detected in 82% (152/186) and 33% (69/212) of any analyzable skin neoplasm, respectively. As regards TMA-2, COX-2 immunoreactivity significantly increased from benign nevi (51%) to primary melanomas (86%) to melanoma metastases (91%; P <0.001). In case of primary melanomas, positive COX-2 staining was associated with advanced Clark levels ( P =0.004) and shorter recurrence free survival ( P =0.0271). COX-2 expression was not associated with overall survival. Accordingly, PPARγ immunoreactivity was significantly increasing from benign nevi (0%) to malignant melanomas (22%) and melanoma metastases (33%; P <0.001). However, PPARγ expression in melanomas was not associated with any of the clinico-pathologic characteristics, including overall survival and tumor recurrence. Conclusions: Expression of the enzyme COX-2 and the transcription factor PPARγ is a common phenomenon during the metastatic process of malignant melanoma, representing possible targets for an anti-inflammatory and anti-proliferative therapy.