Hepatobiliary neuroendocrine neoplasms are rare cancers in humans and dogs. To date, no large-scale primary hepatobiliary neoplasm omics analyses exist in any species. This limits the development of diagnostic biomarkers and targeted therapeutics. Neuroendocrine cancers are a heterogenous group of neoplasms categorized by their tissue-of-origin. Because the anatomic niche of neuroendocrine neoplasms shapes tumor phenotype, we sought to compare the proteomes of 3 canine hepatobiliary neoplasms to normal hepatobiliary tissue and adrenal glands with the objective of identifying unique protein signatures. Protein was extracted from formalin-fixed paraffin-embedded samples and submitted for tandem mass spectroscopy. Thirty-two upregulated and 126 downregulated differentially expressed proteins were identified. Remarkably, 6 (19%) of the upregulated proteins are correlated to non-hepatobiliary neuroendocrine neoplasia and 16 (50%) are functionally annotated within the exosome cellular compartment key to neuroendocrine signaling. Twenty-six (21%) downregulated proteins are enriched in metabolic pathways consistent with alterations in cancer. These results suggests that characteristic neoplastic protein signatures can be gleaned from small data sets using a comparative proteomics approach.
Hepatobiliary neuroendocrine neoplasia is an extremely rare cancer in humans and other species. In humans, neuroendocrine neoplasia of the liver and gallbladder represents less than 2% of all gastroenteropancreatic neuroendocrine neoplasia. In the veterinary literature, there is a paucity of information on hepatobiliary neuroendocrine cancer with only a small number of published studies. Improved characterization of these tumors is needed to identify additional biomarkers for diagnosis and generate informed treatment protocols for human and veterinary patients. Here, we applied a proteomics strategy to identify differentially expressed proteins in canine hepatobiliary neoplasia as compared to normal canine adrenal and liver tissue from formalin‐fixed paraffin‐embedded samples. Our objective was to identify unique protein biomarkers and possible chemotherapeutic targets. Thirty‐four up‐regulated, differentially expressed proteins were identified in the hepatobiliary neuroendocrine neoplasia samples. Galectin‐1, a multivalent carbohydrate binding protein known to play a role in lung and pancreatic neuroendocrine neoplasia development and progression, was among them. Drugs targeting the galectin family have shown promise as anticancer therapeutics in cervical cancer, prostate cancer, lung and pancreatic neuroendocrine neoplasia. Galectin‐1 may represent a novel treatment target in hepatobiliary neuroendocrine neoplasia in both humans and dogs.
We have previously demonstrated by the indirect immunofluorescence test that sera of some patients with malignant melanoma contain antibodies to antigens associated with nucleoli of their own and homologous melanoma cells. These studies have shown a correlation between the presence of nucleolar antigen in tumor cells of a melanoma patient, progressive tumor growth, and poor prognosis. The present study was undertaken to determine if nucleoli of melanoma cells possess any unusual morphological features and to demonstrate the nucleolar antigen at the light and electron microscope level by the immunoperoxidase reaction.Melanoma cells from selected patients were examined by electron microscopy after growth in tissue culture.
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