Expression of chromogranins A, B, and C (secretogranin II) in human adrenal medulla and in benign and malignant pheochromocytomas - An immunohistochemical study with region-specific antibodies

In a recent immunohistochemical study of pheochromocytomas, a difference was observed between benign and malignant pheochromocytomas in their expression in different parts of the chromogranin (Cg) A molecule. The purpose of the present study was to extend the investigations by including two other members of this Cg family, CgB and C. Twenty-five patients operated on for clinicopathologically benign pheochromocytomas, and four for metastasizing pheochromocytomas, were studied. Expression of the different Cg regions was studied immunohistochemically by means of region-specific antibodies: four raised against CgA epitopes, five against CgB, and two against CgC. Adrenal medulla parenchyma from three surgical adrenalectomy specimens was used as non-neoplastic control. All cells of normal adrenal medulla were immunoreactive to all 11 region-specific Cg antibodies. In the pheochromocytomas, variations in the expression pattern occurred, but no significant quantitative differences were noted between benign and malignant tumours. Nevertheless, in all four malignant pheochromocytomas, the antibodies raised against the C-terminal regions of both CgB and CgC visualised a noticeable population of large spindle-shaped tumour cells, characterised by elongated processes. This cell type occurred in all four malignant pheochromocytomas but only in one benign tumour. Their structure and immunoreactivity differed from those of the sustentacular cells in the pheochromocytoma parenchyma. The use of region-specific antibodies raised against epitopes in the C-terminal region of CgB and CgC can facilitate the diagnosis of malignant pheochromocytoma.