Expression of the novel inhibitor of apoptosis survivin in normal and neoplastic skin

Apoptosis plays a fundamental part in epidermal homeostasis, and apoptotic cells have been detected in normal and diseased skin. Little is known, howe ver, on the inhibitory mechanisms of apoptosis at the skin level. In additi on to bcl-2, a novel inhibitor of apoptosis designated survivin and structu rally analogous to IAP apoptosis inhibitors has been recently identified. T he expression of survivin in normal and pathologic skin was investigated. I mmunohistochemical studies revealed that survivin is expressed in basal ker atinocytes, but not in suprabasal epidermal layers, with a pattern similar to bcl-2, In western blots, the anti-survivin antibody recognized a single band of 16.5 kDa in protein extracts from normal human keratinocytes in cul ture, in agreement with the predicted size of survivin. In addition, surviv in immunoreactivity was detected in benign and malignant melanocytic lesion s, with strong expression in invasive lesions of melanomas. Whereas survivi n staining was undetectable in benign epithelial tumors, such as seborrheic keratoses, it was observed in all epidermal layers in Bowen's disease. Int erestingly, at variance with bcl-2, survivin was markedly expressed in squa mous cell carcinoma, but virtually lacking in basal cell carcinoma, suggest ing that these two apoptosis inhibitors may act through different anti-apop totic pathways. Deregulation of survivin may influence both epidermal homeo stasis and the development of melanoma and nonmelanoma skin cancer.