Activated Stat-3 in Melanoma

BACKGROUND: Recent studies have demonstrated that the Src-Stat pathway may play an important role in melanoma. We examined the expression of phosphorylated Stat-3 (pStat-3), activated Stat-1 (pStat-1) and interferon alpha receptor subunit 1(IFNAR-1) in human melanocytic neoplasms. METHODS: Compound nevi (6), dysplastic nevi (4), congenital nevi (2), primary melanoma (14), and sentinel lymph node metastasis (40) were examined. Specimens were evaluated for phospho-Stat-1 (pStat-1), phospho-Stat-3 (pStat-3), and IFNAR-1 by immunohistochemistry. Staining was scored from 1 to 3 based on a composite score that took into account both the percentage of tumor cells staining and the intensity of stained cells. RESULTS: Normal melanocytes or benign nevi expressed little pStat-1, pStat-3, or IFNAR-1. In primary cutaneous melanoma, 6 of 14 skin biopsies showed activated Stat-3. However, in melanoma metastatic to regional lymph nodes, 16 of 26 had activated Stat-3 but only 6 of 23 had activated Stat-1. Melanoma tumors had high levels of either pStat-3 or pStat-1 but not both. All melanoma specimens but not benign melanocytes had cytoplasmic IFNAR-1 staining. An increase in Stat-3 activity was seen in melanoma but not in benign nevi or skin melanocytes. There appeared to be an inverse correlation between the levels of pStat-3 and pStat-1 in a given specimen. CONCLUSIONS: The relationship between activated Stat-3 and biological behavior of melanocytic lesions observed in this study warrants further exploration.