Synaptophysin and neurofilament proteins as markers for neuroendocrine tumors

Synaptophysin, a membrane glycoprotein of presynaptic vesicles, and neurofilament (NF) proteins were tested as immunohistochemical markers for neuroendocrine tumors. Synaptophysin was consistently present in the tumor cells of pheochromocytomas (10/10), thyroid medullary carcinomas (8/8), and pancreatic islet cell tumors (6/6). Most gastrointestinal and thoracic carcinoid tumors (12/13) were positive, as were neuroendocrine carcinomas (7/9), of which two Merkel cell carcinomas were negative. The NF proteins were present in all pheochromocytomas, in three thoracic and one gastric carcinoid tumors, in four of eight thyroid medullary carcinomas, and in five of six pancreatic islet cell tumors. All intestinal carcinoids were negative for NF proteins, as were neuroendocrine carcinomas, except for two Merkel cell carcinomas that were positive. The 68-kilodalton (kd) NF subunit protein was the most prevalent in all NF-positive neuroendocrine tumors, and the 160-kd subunit was relatively often present, although in a smaller number of cells. The 200-kd NF subunit protein was regularly found in pheochromocytomas and only occasionally found in other neuroendocrine tumors. A series of nonneuroendocrine tumors, such as adenocarcinomas, sarcomas, lymphomas, and melanomas, were negative for both synaptophysin and NF proteins. Thus, synaptophysin is a specific and fairly sensitive marker for neuroendocrine tumors of both low and high grades of malignancy. The NF proteins are good markers for pheochromocytoma, and their presence is of basic tumor biologic interest and of potential diagnostic value in other neuroendocrine neoplasms.