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Catecholamine-Synthesizing Enzymes in Carcinoid Tumors and Pheochromocytomas

Departments of
¹ Medical Oncology,
² Medical Physiology,
³ Pathology and Laboratory Medicine, and
⁴ Endocrinology, University Hospital Groningen, 9700 RB Groningen, The Netherlands.

^aAddress correspondence to this author at: Department of Medical Oncology, University Hospital, PO Box 30.001, 9700 RB Groningen, The Netherlands. Fax 31-503614862; e-mail e.g.e.de.vries{at}int.azg.nl.

Background: Serotonin is the principal endocrine product of carcinoid tumors, but simultaneously increased production of catecholamines has been described in these tumors. As it is not clear whether these tumors contain specific enzymes for catecholamine synthesis, we aimed to detect catecholamine-synthesizing enzymes [tyrosine hydroxylase (TH), dopamine-ß-hydroxylase (DBH), and phenylethanolamine-N-methyltransferase (PNMT)] in midgut carcinoid tumors and pheochromocytoma and to correlate enzyme expression to serotonin production as well as catecholamines and metabolites excreted in urine.

Methods: Paraffin-embedded tumor specimens from 21 midgut carcinoid patients and 20 pheochromocytoma patients (10 sporadic and 10 MEN type IIa-related tumors) were stained for TH, DBH, and PNMT, using a three-step biotin-avidin-peroxidase method.

Results: TH was demonstrated in 9 (43%) of 21 carcinoids and in all (100%) of 20 pheochromocytomas, DBH in 8 (38%) carcinoids and in 15 (75%) pheochromocytomas, and PNMT in 7 (33%) carcinoids and in 13 (65%) pheochromocytomas. Increased urinary excretion of catecholamines and metabolites was observed in 10 (48%) carcinoid patients and in all pheochromocytoma patients. No clinically relevant association between enzyme expression and urinary excretion of catecholamines and metabolites was found.

Conclusions: Catecholamine-synthesizing enzymes are present in many carcinoid tumors. This finding possibly indicates the existence of a catecholamine-synthesizing pathway in carcinoids similar to that found in pheochromocytoma.

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