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.
Messina
Jane L
JL
Pathology Service, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA. jane.messina@moffitt.org
Yu
Hua
H
Riker
Adam I
AI
Munster
Pamela N
PN
Jove
Richard L
RL
Daud
Adil I
AI
D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000096:biosynthesis; D001706:Biopsy; D018450:Disease Progression; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008544:Melanocytes / Q000378:metabolism / Q000473:pathology; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology; D008875:Middle Aged; D011379:Prognosis; D053633:Receptor, Interferon alpha-beta / Q000096:biosynthesis; D012189:Retrospective Studies; D050796:STAT3 Transcription Factor / Q000096:biosynthesis*; D012878:Skin Neoplasms / Q000378:metabolism* / Q000473:pathology
D014408:Biomarkers, Tumor; C507964:IFNAR1 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D053633:Receptor, Interferon alpha-beta