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Annals of Surgical Oncology, Vol 6, Issue 6 604-608, Copyright © 1999 by Society of Surgical Oncology

ARTICLES

Interferon regulatory factor-1 and -2 expression in human melanoma specimens

J. K. Lowney, L. D. Boucher, P. E. Swanson and G. M. Doherty
Department of Surgery, Washington University, St. Louis, Missouri 63110, USA.

BACKGROUND: Interferon regulatory factor (IRF)-1 and IRF-2 are nuclear transcription factors that respond to interferon-gamma. IRF-1 acts as the effector arm of the interferon-gamma response in tumor cells, whereas IRF-2 binds to the same DNA consensus sequence and opposes IRF-1 activity. This effect is intact in human and murine tumor models, including melanomas; previous work in our laboratory demonstrated the tumor-suppressing activity of IRF-1 expression in in vivo models and the opposing effect of IRF-2. The expression of IRF-1 and -2 in human solid tumors had not been previously investigated. METHODS: Formalin-fixed, paraffin-embedded, archival tissue specimens from 38 human melanomas were obtained and stained with polyclonal anti-IRF-1 and anti-IRF-2 antibodies, using an avidin-biotin-peroxidase complex technique with epitope retrieval. RESULTS: Twenty-nine specimens showed granular cytoplasmic staining with the anti-IRF-1 or anti-IRF-2 antibodies. IRF-1 staining was correlated with less advanced disease. Superficial spreading and in situ lesions exhibited more frequent IRF-1 staining, compared with nodular or metastatic disease. Only more advanced lesions showed neither IRF-1 nor IRF-2 staining. CONCLUSIONS: Immunohistochemical staining of archival tissue identified IRF-1 and -2 in human melanomas; this had not been previously demonstrated. IRF-1 staining was correlated with the morphologic characteristics of less advanced disease. Tumor-suppressing effects of IRF-1 may account for the less aggressive biologic features of IRF-1-expressing melanomas, as we would predict from the experimental data.


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