Immunohistochemical, biochemical and immunoelectron microscopic analysis of antigenic proteins on neuroendocrine cell tumors using monoclonal antibody HISL-19.

The monoclonal antibody HISL-19 was originally generated after immunizing BALB/c mice with human islet cells. We used this antibody to study a wide variety of neuroendocrine (NE) and non-NE tumors by immunohistochemical, immunoelectron microscopic, and biochemical (Western blotting) techniques. Of the thyroid tumors, HISL-19 specifically immunoreacted with medullary carcinoma of the thyroid (MCT); of the pancreatic tumors, it reacted with islet cell tumors such as insulinomas and a gastrinoma; of the adrenal tumors, it reacted with pheochromocytoma. HISL-19 showed particularly strong immunoreactivity to a gross granular material at the perinuclear area in the MCT and malignant pheochromocytoma but not in the benign pheochromocytoma, although the latter cells showed a faint and homogenous positive reactivity in the cytoplasm. The strongly HISL-19-positive material was found to consist of newly synthesized antigenic proteins with a molecular weight between 60 and 65 kilodaltons (kDa) by Western blotting. Immunoelectron microscopic analysis revealed that this antigenic protein was located in the secretory granules that appear markedly in malignant endocrine tumors, usually located close to the nucleus. Thus, HISL-19 is a useful and specific marker for the immunohistochemical diagnosis of NE cell tumors. The specific antigenic proteins of HISL-19 were defined in MCT and malignant pheochromocytoma. These proteins are speculated to be actively synthesized and more highly produced in the secretory granules of malignant endocrine tumors than benign ones. Thus, a preoperative immunohistochemical study using HISL-19 might be useful for predicting the grade of malignancy of endocrine malignant tumors and thus help determine an appropriate operative procedure, in addition to being a useful marker of neuroendocrine cell tumors.