Summary
Immunohistochemical localization of the catecholamine synthesizing enzymes, tyrosine hydroxylase (TH), aromatic L-amino acid decarboxylase (AADC), dopamine-β-hydroxylase (DBH) and phenylethanolamineN-methyltransferase (PNMT), was investigated in 70 cases of functioning and non-functioning phaeochromocytomas comprising 52 of adrenal and 18 of extra-adrenal origin. Of 59 functioning tumours, 30 were mixed epinephrine and norepinephrine-producing (mixed type) and 29 were norepinephrine-producing tumours. TH, AADC and DBH were detected in all functioning phaeochromocytomas, but PNMT was limited to the mixed-type phaeochromocytomas. Non-functioning phaeochromocytomas were divided into two groups, comprising a complete type, which induced neither elevated plasma catecholamines nor their metabolites in urine, and an incomplete type which exhibited no elevated plasma catecholamines, but showed a slightly high urinary vanillylmandelic acid level. In the non-functioning complete-type tumours, immunoreactive TH was negative, but the incomplete tumours of the adrenal medulla had all four enzymes, and corresponded to a mixed-type phaeochromocytoma. AADC and DBH were present universally in all functioning and non-functioning tumours, including TH-negative tumours. TH is a rate-limiting enzyme of catecholamine biosynthesis and deficiency of TH is an important feature of extraadrenal non-functioning phaeochromocytomas.
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References
Eränko O, Lempinen M, Räisänen L (1966) Adrenaline and noradrenaline in the organ of Zuckerkandl and adrenals of newborn rats treated with hydrocortisone. Acta Physiol Scand 66:253–254
Gazdar AF, Helman LJ, Israel MA, Russell EK, Linnoila I, Mulshine JL, Schuller HM, Park J-G (1988) Expression of neuroendocrine cell marker L-dopa decarboxylase, chromogranin A, and dense core granules in human tumors of endocrine and neuroendocrine origin. Cancer Res 48:4078–4082
Goldstein M, Fux K, Hokfelt T, Joh TH (1971) Immunohistochemical studies on phenylethanolamine N-methyltransferase, dopa decarboxylase and dopamine-hydroxylase. Experientia 27:951–952
Han VKM, Snouweart J, Towle AC, Lund PK, Lauder JM (1987) Cellular localization of tyrosine hydroxylase mRNA and its regulation in the rat adrenal medulla and brain by in situ hybridization with an oligodeoxyribonucleotide probe. J Neurosci Res 17:11–18
Kimura N (1991) Functioning and non-functioning adrenal medullary tumors. Endocr Pathol 2:64–73
Kimura N, Sasano N (1990) A comparative study between malignant and benign pheochromocytoma using morphometry, cytophotometry, and immunohistochemistry. In: Lechago J, Kameya T (eds) Endocrine pathology update. Field and Wood, New York, pp 99–118
Kimura N, Sasano N, Miura Y, Kobayashi K (1984) Adrenal and extra-adrenal pheochromocytomas: an ultrastructural and formaldehyde-induced fluorescence study with catecholamine content. Tohoku J Exp Med 142:1–14
Kimura N, Sasano N, Yamada R, Satoh J (1988) Immunohistochemical study of chromogranin in 100 cases of pheochromocytoma, carotid body tumor, medullary thyroid carcinoma and carcinoid tumor. Virchows Arch [A] 413:3–10
Kimura N, Nakazato Y, Nagura H, Sasano N (1990) Expression of intermediate filaments in neuroendocrine tumors. Arch Pathol Lab Med 114:506–510
Kimura N, Miura Y, Miura K, Takahashi N, Osamura RY, Nagatsu I, Nagura H (1991) Adrenal and retroperitoneal mixed neuroendocrine and neural tumours. Endocr Pathol 2:139–147
Lloyd RV, Sisson JC, Shapiro B, Verhoffsfad AAJ (1986) Immunohistochemical localization of epinephrine, norepinephrine, catecholamine-synthesizing enzymes, and chromogranin in neuroendocrine cells and tumors. Am J Pathol 125:45–54
Nagatsu I, Kondo Y (1974) Immunoelectron microscopic localization of phenylethanol-amine-N-methyltransferase in the bovine adrenal medulla. Histochemistry 42:351–358
Nagatsu I, Sakai M, Yoshida M, Nagatsu T (1988) Aromaticl-amino acid decarboxylase-immunoreactive neurons in and around the cerebrospinal fluid-contacting neurons of the central canal do not contain dopamine or serotonin in the mouse and rat spinal cord. Brain Res 475:91–102
Osamura RY, Yasuda O, Kawai K, Hori S, Suemizu H, Onoda N, Joh TH (1990) Immunohistochemical localization of catecholamine-synthesizing enzymes in human pheochromocytomas. Endocr Pathol 1:102–108
Schalling M, Dagerlind A, Bren S, Petterson R, Kvist S, Brownstein M, Hyman SE, Mucke L, Goodman HM, Joh TH, Goldstein M, Hokfelt T (1987) Localization of mRNA for phenylethanolamineN-methyltransferase (PNMT) using in situ hybridization. Acta Physiol Scand 131:531–632
Schröder S, Padberg B, Achilles E, Grabe E, Dralle H, Klöpper G (1990) Immunocytochemical and DNA cytophotometrical findings in adrenal pheochromocytoma (PCC). Acta Endocrinol (Copenh) 122 [Suppl 1]:1
Takahashi H, Nakashima S, Kumanishi T, Ikuta F (1987) Paragangliomas of the craniocervical region. An immunohistochemical study on tyrosine hydroxylase. Acta Neuropathol (Berl) 73:227–232
Verhofstad AAJ, Häkfeit T, Goldstein M, Steinbusch HWM, Joosten HWJ (1979) Appearance of tyrosine hydroxylase, aromatic amino-acid decarboxylase, dopamine-β-hydroxylase and phenyl-ethanolamineN-methyltransferase during the ontogenesis of the adrenal medulla. Cell Tissue Res 200:1–13
Verhofstad AAJ, Steinbusch HWM, Joosten HWJ, Penke B, Varga J, Goldstein M (1983) Immunocytochemical localization of noradrenalin, adrenalin and serotonin. In: Polak JM, Van Noorden S (eds) Immunocytochemistry: practical applications in pathology and biology. Wright PSG, Bristol, pp 143–168
Wurtman RJ, Axelrod J (1966) Control of enzymatic synthesis of adrenalin in the adrenal medulla by adrenal cortical steroids. J Biol Chem 241:2301–2308
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Kimura, N., Miura, Y., Nagatsu, I. et al. Catecholamine synthesizing enzymes in 70 cases of functioning and non-functioning phaeochromocytoma and extra-adrenal paraganglioma. Vichows Archiv A Pathol Anat 421, 25–32 (1992). https://doi.org/10.1007/BF01607135
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DOI: https://doi.org/10.1007/BF01607135