EFFECT OF INTERFERON-ALPHA ON THE EXPRESSION OF TUMOR-NECROSIS-FACTOR-ALPHA BY METASTATIC MALIGNANT-MELANOMA IN-VIVO

To our knowledge modulation of the expression of tumour necrosis facto r-alpha (TNF-alpha) in malignant melanoma metastases in vivo has not b een reported. The expression of TNF-alpha by malignant melanoma cells was studied immunohistochemically using an anti-TNF-alpha antibody. Th e specificity of the staining reaction was demonstrated by absorption of the TNF-alpha antibody with human recombinant TNF-alpha, which inhi bited the staining reaction. The TNF-alpha expression was also verifie d by in situ hybridization for mRNA. Metastases from 37 patients were studied, 21 of whom were treated with IFN-alpha. All 16 metastases fro m untreated patients were positive for TNF-alpha. Based on the average staining intensity of the melanoma cells for TNF-alpha, the metastase s were classified into two groups. The expression of TNF-alpha varied considerably between metastases from different patients and also withi n the same metastasis. Melanoma cells in areas with row cellularity an d large numbers of infiltrating inflammatory cells were generally weak ly stained. This is in good agreement with a low staining score for TN F-alpha in metastases showing marked histopathological regression. Sev en out of 13 patients with a low staining score for TNF-alpha showed a marked regression of their tumours. In contrast one out of five patie nts with a high staining score for TNF-alpha showed a marked tumour re gression, suggesting that tumour cells sensitive to immune-mediated re gression express less TNF-alpha. Interferon-alpha (IFN-alpha) appears to modulate the expression of TNF-alpha. Significantly more patients t reated with IFN-alpha had metastases with a low TNF-alpha staining sco re compared with untreated patients. Thus, seven out of 21 patients tr eated with IFN-alpha showed a high expression of TNF-alpha in contrast to 13 out of 16 in the untreated group (P=0.01).