Granins and their derived
peptides are valuable circulating
biological markers of
neuroendocrine tumors. The aim of the present study was to investigate the tumoral
chromogranin A (CgA)-derived
peptide WE-14 and the potential advantage to combine plasma WE-14 detection with the EM66 assay and the existing current CgA assay for the diagnosis of
pheochromocytoma. Compared to healthy volunteers, plasma WE-14 levels were 5.4-fold higher in patients with
pheochromocytoma, but returned to normal values after surgical resection of the
tumor. Determination of plasma CgA and EM66 concentrations in the same group of patients revealed that the test assays for these markers had an overall 84% diagnostic sensitivity, which is identical to that determined for WE-14. However, we found that WE-14 measurement improved the diagnostic sensitivity when combined with the results of CgA or EM66 assays. By combining the results of the three assays, the sensitivity for the diagnosis of
pheochromocytoma was increased to 95%. In fact, the combination of WE-14 with either CgA or EM66 test assays achieved 100% sensitivity for the diagnosis of
paragangliomas and sporadic or malignant
pheochromocytomas if taken separately to account for the heterogeneity of the
tumor. These data indicate that WE-14 is produced in
pheochromocytoma and secreted into the general circulation, and that elevated plasma WE-14 levels are correlated with the occurrence of this chromaffin cell
tumor. In addition, in association with other
biological markers, such as CgA and/or EM66, WE-14 measurement systematically improves the diagnostic sensitivity for
pheochromocytoma. These findings support the notion that
granin-processing products may represent complementary tools for the diagnosis of
neuroendocrine tumors.