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PPAR Research
Volume 2010, Article ID 848645, 11 pages
http://dx.doi.org/10.1155/2010/848645
Research Article

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

1Department of Dermatology, University of Regensburg, 93042 Regensburg, Germany
2Department of Hematology and Oncology, University of Regensburg, 93042 Regensburg, Germany
3Institute of Pathology, University of Regensburg, 93042 Regensburg, Germany
4Institute of Pathology, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany
5Institute of Clinical Pathology, University of Erlangen, 91054 Erlangen, Germany
6OncoRay - Center for Radiation Research in Oncology, TU Dresden, 01307 Dresden, Germany
7Institute of Surgical Pathology, University Hospital Zurich, Schmelzbergstrasse 12, 8091 Zurich, Switzerland

Received 10 March 2009; Accepted 14 April 2009

Academic Editor: Dipak Panigrahy

Copyright © 2010 Stefanie Meyer et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

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 ( ) from 47 organs including skin neoplasms ( ); 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.