Interferon regulatory factor-1 and -2 expression in human melanoma specimens.
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.
Lowney
J K
JK
Department of Surgery, Washington University, St. Louis, Missouri 63110, USA.
Boucher
L D
LD
Swanson
P E
PE
Doherty
G M
GM
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000906:Antibodies / Q000032:analysis; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D050856:Interferon Regulatory Factor-1; D050836:Interferon Regulatory Factor-2; D007371:Interferon-gamma / Q000378:metabolism*; D008297:Male; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology; D008875:Middle Aged; D010750:Phosphoproteins / Q000378:metabolism*; D011379:Prognosis; D012097:Repressor Proteins; D012878:Skin Neoplasms / Q000378:metabolism* / Q000473:pathology; D014157:Transcription Factors
D000906:Antibodies; D004268:DNA-Binding Proteins; C494257:IRF1 protein, human; C494229:IRF2 protein, human; D050856:Interferon Regulatory Factor-1; D050836:Interferon Regulatory Factor-2; D010750:Phosphoproteins; D012097:Repressor Proteins; D014157:Transcription Factors; D007371:Interferon-gamma