Research article: Cyclooxygenase 2 (COX2) and peroxisome proliferator-activated receptor gamma (PPARG) are stage-dependent prognostic markers of malignant melanoma

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 primarymmand 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. copyright © 2010 stefanie meyer et al.