Peroxisome proliferator-activated receptor gamma is a member of the nuclear receptor superfamily involved in adipocyte differentiation and glucose homeostasis. There is evidence that peroxisome proliferator-activated receptor gamma may also act as a tumor suppressor. Here, we demonstrate expression of peroxisome proliferator-activated receptor gamma in benign melanocytic naevi, different variants of primary cutaneous melanomas, and melanoma metastases. Peroxisome proliferator-activated receptor gamma protein and peroxisome proliferator-activated receptor gamma1 mRNA were also detected in human melanoma cell lines. The peroxisome proliferator-activated receptor gamma specific agonists 15-deoxy-Delta12,14-prostaglandin J2, troglitazone, and rosiglitazone dose-dependently inhibited cell proliferation in four melanoma cell lines, whereas a specific agonist of peroxisome proliferator-activated receptor alpha had no such effect. At a concentration of 50 microM rosiglitazone, the most potent peroxisome proliferator-activated receptor gamma agonist tested suppressed cell growth by approximately 90%. Apoptosis could be induced in melanoma cell lines by incubation with tumor-necrosis-factor-related apoptosis-inducing ligand. In contrast, the growth inhibitory effect of peroxisome proliferator-activated receptor gamma activation was independent of apoptosis and seemed to occur primarily through induction of cell cycle arrest. Our data indicate that melanoma cell growth may be modulated through peroxisome proliferator-activated receptor gamma.

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Early detection of melanoma metastases is essential for effective treatment and may be crucial for the prevention of systemic metastases and patient survival. However, data demonstrating the reliability and accuracy of ultrasound examination for the detection of lymph node metastases, in addition to clinical examination, are rare. We have examined 433 melanoma patients with stage-dependent follow-up intervals of 3 to 12 months. One thousand three hundred and thirty-two paired clinical and nonblinded sonographic tests of the locoregional lymph node areas were performed. Lesions suspicious of melanoma metastases were examined histopathologically. Of note, sensitivity [0.9394 (95% confidence interval: 0.7977-0.9926)] and specificity [0.9808 (95% confidence interval: 0.9717-0.9875)] of combined clinical and sonographic investigations were significantly (P<0.0001) higher than clinical results alone. Significant differences between clinical follow-up and sonographically assisted follow-up were found for American Joint Committee on Cancer 2002 melanoma stages I (P=0.0389), III (P=0.0101), and IV (P=0.0016). For stage II melanoma, a trend was detected (P=0.0821). Lymph node metastases were detected sonographically in 1.73% of clinically metastasis-free investigations (n=22). Our data suggest that high-frequency sonography should be part of all melanoma follow-up investigations, independent of melanoma type, melanoma stage, or lymph node biopsy status.

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