Catecholamine-synthesizing enzymes in carcinoid tumors and pheochromocytomas.
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-beta-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.
Meijer
Wim G
WG
Department of Medical Oncology, University Hospital Groningen, The Netherlands.
Copray
Sjef C V M
SC
Hollema
Harry
H
Kema
Ido P
IP
Zwart
Nynke
N
Mantingh-Otter
Ietje
I
Links
Thera P
TP
Willemse
Pax H B
PH
de Vries
Elisabeth G E
EG
D000310:Adrenal Gland Neoplasms / Q000201:enzymology* / Q000378:metabolism; D000328:Adult; D002276:Carcinoid Tumor / Q000201:enzymology* / Q000378:metabolism; D002395:Catecholamines / Q000096:biosynthesis* / Q000652:urine; D004299:Dopamine beta-Hydroxylase / Q000096:biosynthesis; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000201:enzymology* / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D010625:Phenylethanolamine N-Methyltransferase / Q000096:biosynthesis; D010673:Pheochromocytoma / Q000201:enzymology* / Q000378:metabolism; D012701:Serotonin / Q000096:biosynthesis / Q000652:urine; D014446:Tyrosine 3-Monooxygenase / Q000096:biosynthesis
D002395:Catecholamines; D012701:Serotonin; D014446:Tyrosine 3-Monooxygenase; D004299:Dopamine beta-Hydroxylase; D010625:Phenylethanolamine N-Methyltransferase