Cyclooxygenase 2 (COX2) and Peroxisome Proliferator-Activated Receptor Gamma (PPARG) Are Stage- Dependent Prognostic Markers of Malignant Melanoma

• Published in: PPAR Research 2010-01, Vol.2010 (2010), p.662-672
• Main Authors: Meyer, Stefanie, Vogt, Thomas, Landthaler, Michael, Berand, Anna, Reichle, Albrecht, Bataille, Frauke, Marx, Andreas H., Menz, Anne, Hartmann, Arndt, Kunz-Schughart, Leoni A., Wild, Peter J.
• Format: Article
• Language: English
• Subjects: Cancer therapies; Skin cancer; Studies; Tumors
• ISSN: 1687-4757; 1687-4765
• DOI: 10.1155/2010/848645

Using tissue microarrays (TMAs) we studied COX2/PPARG immunoreactivity in a broad spectrum of tumors focussing on clinicopathological correlations and the outcome of patients with malignant melanoma (MM). TMA-1 contained normal and tumor tissues (n=3448) from 47 organs including skin neoplasms (n=323); TMA-2 88 primary MM, 101 metastases, and 161 benign nevi. Based on a biomodulatory approach combining COX/PPAR-targeting with metronomic low-dose chemotherapy metastases of 36 patients participating in a randomized trial with metastatic (stage IV) melanoma were investigated using TMA-3. COX2/PPARG immunoreactivity significantly increased from nevi to primary MM and metastases; COX2 positivity was associated with advanced Clark levels and shorter recurrence-free survival. Patients with PPARG-positive metastases and biomodulatory metronomic chemotherapy alone or combined with COX2/PPARG-targeting showed a significantly prolonged progression-free survival. Regarding primary MM, COX2 expression indicates an increased risk of tumor recurrence. In metastatic MM, PPARG expression may be a predicitive marker for response to biomodulatory stroma-targeted therapy.