ASSOCIATION OF TUMOR-NECROSIS-FACTOR-ALPHA GENE-EXPRESSION AND APOPTOTIC CELL-DEATH WITH REGRESSION OF SHOPE PAPILLOMAS

The objective of this study was to test the hypothesis that spontaneou s regression of Shope papillomas involves tumor necrosis factor-alpha and apoptotic cell death of the papilloma cells. In situ hybridization using RNA probes of rabbit tumor necrosis factor-alpha revealed tumor necrosis factor-alpha mRNA in most of the numerous mononuclear cells infiltrating the upper dermis of regressing papillomas and at the derm oepidermal junction. Such cells in progressing papillomas were much fe wer in number and were located in the deeper dermis. In situ terminal deoxynucleotidyl transferase assay demonstrated DNA strand breaks in m any scattered epidermal keratinocytes of regressing papillomas but in only a few thin layers just beneath the horny layer in progressing pap illomas. Electron microscopy demonstrated that regressing papillomas c ontained many apoptotic bodies and keratinocytes showing apoptotic cha nges such as chromatin condensation, degradation of condensed nuclei, surface protuberances, and a filamentous degeneration, as well as infi ltrating lymphocytes and macrophages. We propose that tumor necrosis f actor-alpha produced by infiltrating mononuclear cells probably plays a role in the papilloma regression.