Variable expression of tumor necrosis factor α in human malignant melanoma localized by in situ hybridization for mRNA

Tumor necrosis factor α (TNFα) is a cytokine, produced by lymphocytes and monocytes, with cytotoxic activity against some but not all tumor cell lines. Resistance to the cytolytic effects of TNFα has been reported in cell lines with autocrine TNFα production. The purpose of this study was to investigate whether human primary malignant melanoma and tumor infiltrating lymphocytes produce TNFα in vivo. Optimal conditions for in situ hybridization for TNFα mRNA in paraffin-embedded tissue were established. Analysis of 13 primary malignant melanomas and 3 metastatic lesions with different degrees of immunohistochemical TNFα positivity demonstrated that, in some tumors, both melanoma cells and leukocytes contained TNFα mRNA and protein. These findings demonstrate variable production of TNFα in primary and metastatic melanoma in vivo.The previously described resistance to TNFα cytolytic activity may, therefore, be clinically important.