Decreased expression of neuropeptides in malignant paragangliomas: An immunohistochemical study

Abstract

Paraffin-embedded sections of 99 human adrenal and extraadrenal paragangliomas were analyzed by the indirect immunoperoxidase technique for the presence of neuron-specific enolase (NSE) and 10 neuropeptides. Each showed diffuse staining for NSE. Most tumors were positive for [Leu5]-enkephalin (76 per cent), [Met5]-enkephalin (75 per cent), somatostatin (67 per cent), and pancreatic polypeptide (51 per cent), followed by vasoactive intestinal polypeptide (VIP) (43 per cent), substance P (31 per cent), ACTH (28 per cent), calcitonin (23 per cent), bombesin (15 per cent), and neurotensin (12 per cent). The neuropeptides paralleled to a large extent those normally found in the sympathetic nervous system. Clinically malignant paragangliomas (n = 25) with proven regional or distant metastases expressed considerably fewer neuropeptides, although the spectrum of those seen remained similar. Malignant paragangliomas contained an average of two neuropeptides per tumor, in contrast to five for the benign tumors (P less than 0.05). Logistic regression analysis of staining results revealed that the paucity of enkephalins, somatostatin, pancreatic polypeptide, and VIP along with the patient's sex was predictive of clinical malignancy. Our results show a definite relationship between expression of neuropeptides and the biologic behavior of these paragangliomas.