Survivin expression in canine and feline cancer
Johnson, Melanie E.
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Survivin is an inhibitor of apoptosis protein that is expressed during embryonic development and several human malignancies but is absent in most adult tissues. Its expression is often associated with a more malignant phenotype and decreased response to chemotherapeutics. Analysis of the expression profile of transcripts in various cancers identified survivin as one of the top four transcripts upregulated in malignancy. Four human survivin isoforms have been identified that differ in their ability to inhibit apoptosis. Thus, these isoforms may represent a regulatory balance between apoptosis and inhibition of apoptosis. Intense research is currently under way in human medicine to investigate the role of survivin in cancer. However, nothing is known in regards to survivin expression in veterinary species. In order to examine survivin expression in canine and feline tissues, immunohistochemistry (IHC) and RT-PCR were performed on dog and cat embryos, normal adult tissues, inflammatory and hyperplastic tissues, and a variety of neoplastic tissues. Survivin was expressed in fetal tissues, some hyperplastic, inflammatory, and neoplastic tissues, but was absent in most normal, adult tissues. To determine its significance as a prognostic parameter in canine cancer, survivin expression was determined in neoplastic lymph nodes from dogs undergoing chemotherapy for lymphosarcoma. Survivin expression was shown to be a negative predictor of survival in canine lymphosarcoma. Canine survivin isoforms have yet to be identified. To explore the possibility of differential expression of canine survivin isoforms, survivin subcellular localization, and proliferative and apoptotic markers were compared between canine mammary adenomas and carcinomas that were all positive for survivin by IHC. Differences in nuclear survivin expression, Ki-67, and caspase-3 between the tumor types were not observed, thus potential expression of different canine survivin isoforms was not apparent from our data. In conclusion, results of this work suggest that survivin expression in veterinary species needs to be further investigated, as this protein may prove to be useful in the diagnosis and prognosis of animal cancers. Furthermore, survivin could potentially become a therapeutic target in veterinary oncology in the future.