Immunohistochemical characterization of intestinal neoplasia in zebrafish Danio rerio indicates epithelial origin

Spontaneous neoplasia of the intestinal tract in sentinel and moribund zebrafish Danio rerio is common in some zebrafish facilities. We previously classified these tumors as adenocarcinoma, small-cell carcinoma, or carcinoma otherwise unspecified based on histomorphologic characteristics. Based on histological presentation, the primary differential diagnosis for the intestinal carcinomas was tumor of neuroendocrine cells (e.g. carcinoids). To further characterize the phenotype of the neoplastic cells, select tissue sections were stained with a panel of antibodies directed toward human epithelial (cytokeratin wide spectrum screening [WSS], AE1/AE3) or neuroendocrine (S100, chromogranin A) markers. We also investigated antibody specificity by Western blot analysis, using a human cell line and zebrafish tissues. Nine of the intestinal neoplasms (64%) stained for AE1/AE3; 7 (50%) also stained for WSS. None of the intestinal neoplastic cells stained for chromogranin A or S100. Endocrine cells of the pituitary gland and neurons and axons of peripheral nerves and ganglia stained for chromogranin A, whereas perineural and periaxonal cells of peripheral intestinal ganglia, and glial and ependymal cells of the brain stained for S100. Immunohistochemistry for cytokeratins confirmed the majority of intestinal neoplasms in this cohort of zebrafish as carcinomas.