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.