Evaluation of plasma 3,4-dihydroxyphenylacetic acid (DOPAC) and plasma 3,4-dihydroxyphenylalanine (DOPA) as tumor markers in children with neuroblastoma

Abstract

Catecholamines and their metabolites are important in the diagnosis of neuroblastoma (NB). Plasma (p-) levels of 3,4-dihydroxyphenylalanine (DOPA) are increased in most NB, probably reflecting decreased DOPA decarboxylase activity. Urine (u-) homovanillic acid (HVA), a DOPA and dopamine (DA) metabolite, is also increased in most NB. DOPAC (3,4-dihydroxyphenylacetic acid) is an important metabolite of DA in tissues with monoamine oxidase (MAO) activity. Because MAO is expressed in NB tumor cells, we studied the importance of measuring p-DOPAC and p-DOPA as compared to u-HVA and u-vanillylmandelic acid (VMA) in the diagnosis and follow-up of NB. DOPAC, DOPA, dopamine, noradrenaline, adrenaline, VMA and HVA were measured by reverse-phase HPLC with electrochemical detection in 106 children (28 with NB (13 newly diagnosed), 25 with other solid tumors, 28 hospitalized for nonneoplastic diseases, and 25 healthy children). P-DOPAC or p-DOPA concentrations were above the upper normal range in 92% of untreated NB patients, as were u-HVA or u-VMA levels. None of these tumor markers was correlated to tumor stage or survival. P-DOPA but not p-DOPAC was correlated to age in NB children. Increased values of p-DOPAC and p-DOPA were found in one patient surviving NB for 10 years. Plasma DOPAC concentrations were decreased in children hospitalized for non-NB diseases, probably reflecting reduced food intake. Plasma analyses of DOPA and DOPAC seem to be useful alternatives in the diagnosis and follow-up of NB if urine sampling is to be avoided. Plasma DOPAC may be an index of nutritional status in various diseases.