Circulating EM66 is a highly sensitive marker for the diagnosis and follow-up of pheochromocytoma.
We have previously demonstrated that measurement of tissue concentration of the novel secretogranin II-derived peptide EM66 may help to discriminate between benign and malignant pheochromocytomas. The aim of the present study was to characterize EM66 in plasma and urine of healthy volunteers and pheochromocytoma patients, in order to further evaluate the usefulness of this peptide as a circulating marker for the management of the tumors. HPLC analysis of plasma and urine samples demonstrated that the EM66-immunoreactive material coeluted with the recombinant peptide. In healthy volunteers, plasma and urinary EM66 levels were, respectively, 2.6 (1.9-3.7) ng/ml and 2.9 (1.9-4.6) ng/ml. In patients with pheochromocytoma, plasma EM66 levels were 10-fold higher than those of healthy volunteers (26.9 (7.3-44) ng/ml), and returned to normal values after removal of the tumor. In contrast, urinary EM66 levels were not significantly different from those of healthy volunteers (3.2 (2.2-3.9) ng/ml). Measurement of total or free plasma metanephrines and 24 hr urinary metanephrines in our series of patients revealed that these tests, taken separately, are less sensitive than the EM66 determination. Pheochromocytes in primary culture secreted high levels of EM66, suggesting that the chromaffin tumor was actually responsible for the increased plasma peptide concentrations in the patients. These data indicate that EM66 is secreted in the general circulation and that elevated plasma EM66 levels are correlated with the occurrence of pheochromocytoma. Thus, EM66 is a sensitive plasma marker that should be considered as a complementary tool in the management of pheochromocytoma.
Guillemot
Johann
J
INSERM U413, Laboratory of Cellular and Molecular Neuroendocrinology, European Institute for Peptide Research (IFRMP 23), University of Rouen, Mont-Saint-Aignan, France.
Anouar
Youssef
Y
Montero-Hadjadje
Maïté
M
Grouzmann
Eric
E
Grumolato
Luca
L
Roshmaninho-Salgado
Joana
J
Turquier
Valérie
V
Duparc
Céline
C
Lefebvre
Hervé
H
Plouin
Pierre-François
PF
Klein
Marc
M
Muresan
Mihaela
M
Chow
Billy K C
BK
Vaudry
Hubert
H
Yon
Laurent
L
D000310:Adrenal Gland Neoplasms / Q000175:diagnosis* / Q000473:pathology*; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood* / Q000652:urine; D016022:Case-Control Studies; D002851:Chromatography, High Pressure Liquid; D002864:Chromogranins / Q000097:blood* / Q000652:urine*; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D007118:Immunoassay; D008297:Male; D008676:Metanephrine; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood* / Q000652:urine; D010673:Pheochromocytoma / Q000175:diagnosis* / Q000473:pathology*; D053381:Secretogranin II / Q000097:blood* / Q000652:urine; D012680:Sensitivity and Specificity
D014408:Biomarkers, Tumor; D002864:Chromogranins; C557436:EM66 peptide; D010446:Peptide Fragments; D053381:Secretogranin II; D008676:Metanephrine