Studies on tyrosine hydroxylase in neuroblastoma, in relation to urinary levels of catecholamine metabolites

Abstract

Tyrosine hydroxylase (TH) activity has been determined in 22 neuroblastoma tumors from 15 patients, in 1 pheochromocytoma, 20 adrenal glands, 10 other tumors and organs, and 4 specimens of sera. The enzyme activity was found only in the neural crest tumors and adrenal glands, but the levels were too low to be detected in the other tumors and in normal liver and kidney tissues. The average specific activity (mean +/- SE) of TH in 23 neural crest tumors was 0.559 +/- 0.101; in 20 adrenal glands was 0.418 +/- 0.124 nmol/mg protein/minute. In 13 patients with neuroblastoma and 1 patient with pheochromocytoma, both TH levels in the primary tumors and urinary excretion of vanillylmandelic acid (VMA) and homovanillic acid (HVA) were studied. The urinary excretion of VMA by 10 of 13 neuroblastoma patients and by the patient with pheochromocytoma was significantly to markedly elevated above normal levels; excretion of HVA by 12 of 13 neuroblastoma patients was similarly elevated. These results indicate that tyrosine hydroxylase, an enzyme specifically located in the adrenal medulla and monoaminergic neurons, is also present in neuroblastoma, a malignant tumor of similar embryologic origin, and in pheochromocytoma. Not only can TH activity in these tumors be demonstrated in vitro, but the elevated urinary excretion of VMA and/or HVA by the majority of patients with these tumors also indicates TH activity of the tumors in vivo.