SYP (Synaptophysin) is a protein associated with neuronal synaptic vesical membranes and it is involved in regulating endocytosis. In immunohistochemistry, SYP acts as a small cell neuroendocrine marker, and it is a very sensitive marker of neuroendocrine differentiation. It is a specific and sensitive marker for well differentiated neuroendocrine tumors, and it is positive in neural tumors, epithelial tumors and tumors with neuroendocrine differentiation. These include neuroblastomas, retinoblastomas, ganglioneuromas, pheochromocytomas, Merkel cell carcinoma, small and non-small cell cancer of the lung, pancreatic islet cell neoplasms, medullary thyroid carcinomas and medulloblastomas, bronchopulmonary and gastrointestinal carcinoids, and parathyroid and pituitary adenomas. In normal tissue, staining for SYP is expected to be cytoplasmic in islets of Langerhans, peripheral nerves, and neuroendocrine cells and neurons in the brain, retina and spinal cord. References: Proc Natl Acad Sci USA. 1986, May.83.10; 3500-3504, PMID: 3010302; Cancers 7/31/2012; 4.3; 777-798, PMID: 24213466; Hum Pathol 1990;21:271, PMID: 2107138; Am J Clin Pathol 2011;135:831, PMID: 21571955