title: Cyclooxygenase 2 (COX2) and Peroxisome Proliferator-Activated Receptor Gamma (PPARG) Are Stage-Dependent Prognostic Markers of Malignant Melanoma.
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 (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.
authors.affiliation: Department of Dermatology, University of Regensburg, 93042 Regensburg, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Meyer
authors.forename: Thomas
authors.initials: T
authors.lastname: Vogt
authors.forename: Michael
authors.initials: M
authors.lastname: Landthaler
authors.forename: Anna
authors.initials: A
authors.lastname: Berand
authors.forename: Albrecht
authors.initials: A
authors.lastname: Reichle
authors.forename: Frauke
authors.initials: F
authors.lastname: Bataille
authors.forename: Andreas H
authors.initials: AH
authors.lastname: Marx
authors.forename: Anne
authors.initials: A
authors.lastname: Menz
authors.forename: Arndt
authors.initials: A
authors.lastname: Hartmann
authors.forename: Leoni A
authors.initials: LA
authors.lastname: Kunz-Schughart
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Wild