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Characterization and plasma measurement of the WE-14 peptide in patients with pheochromocytoma.

Guillemot J, Guérin M, Thouënnon E, Montéro-Hadjadje M, Leprince J, Lefebvre H, Klein M, Muresan M, Anouar Y, Yon L - PLoS ONE (2014)

Bottom Line: Granins and their derived peptides are valuable circulating biological markers of neuroendocrine tumors.However, we found that WE-14 measurement improved the diagnostic sensitivity when combined with the results of CgA or EM66 assays.These findings support the notion that granin-processing products may represent complementary tools for the diagnosis of neuroendocrine tumors.

View Article: PubMed Central - PubMed

Affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), U982, Mont-Saint-Aignan, France ; Normandy University, Normandy, France ; Rouen University, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Institute for Research and Innovation in Biomedicine (IRIB), Mont-Saint-Aignan, France ; Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, Montreal, Quebec, Canada.

ABSTRACT
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.

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CgA levels in the plasma of patients with pheochromocytoma.(A) Scattergram of CgA concentrations in plasma samples of patients with pheochromocytoma before surgical removal of the tumor (preop, +, n = 37). (B) Distribution of CgA preoperative concentrations of patients reported in (A), depending on the adrenal (PHEO, ▴, n = 26) or extra-adrenal (PGL, ▾, n =  11) location of the tumor, the benign (•, n = 32) or malignant (▪, n = 5), and the sporadic (♦, n = 24) or hereditary (•, n = 13) nature of the neoplasms. The grey zone represents the cut-off level for the CgA test assay as indicated by the manufacturer. See legends of Figure 2 for other designations.
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pone-0088698-g003: CgA levels in the plasma of patients with pheochromocytoma.(A) Scattergram of CgA concentrations in plasma samples of patients with pheochromocytoma before surgical removal of the tumor (preop, +, n = 37). (B) Distribution of CgA preoperative concentrations of patients reported in (A), depending on the adrenal (PHEO, ▴, n = 26) or extra-adrenal (PGL, ▾, n =  11) location of the tumor, the benign (•, n = 32) or malignant (▪, n = 5), and the sporadic (♦, n = 24) or hereditary (•, n = 13) nature of the neoplasms. The grey zone represents the cut-off level for the CgA test assay as indicated by the manufacturer. See legends of Figure 2 for other designations.

Mentions: Plasma concentrations of CgA in preoperative patients (n = 37) ranged from 6-780 U/l with a median value of 41 U/l (Figure 3A). CgA concentrations were not significantly different between patients with pheochromocytoma or paraganglioma [46.5 (7-770) vs 38 (6-780) U/l, respectively] (Figure 3B). Similarly, CgA levels were not significantly different between patients with benign or malignant neoplasms [39.5 (6-780) vs 58 (10-770) U/l, respectively] (Figure 3B). In contrast, CgA concentrations were significantly higher in patients with sporadic compared to hereditary tumors [55 (10-780) vs 23 (6-770) U/l, respectively] (p<0.05) (Figure 3B). A positive correlation was found between CgA and WE-14 concentrations in the plasma of patients with pheochromocytoma in which high plasma levels of CgA are associated with high levels of WE-14 (r  =  0.717, p<0.001, n = 37) (Figure 4). In addition, except for malignant pheochromocytomas, WE-14 levels were positively correlated to CgA levels in each group of patients (data not shown). No correlation was found between tumor size and CgA levels (r  =  0.339) (data not shown).


Characterization and plasma measurement of the WE-14 peptide in patients with pheochromocytoma.

Guillemot J, Guérin M, Thouënnon E, Montéro-Hadjadje M, Leprince J, Lefebvre H, Klein M, Muresan M, Anouar Y, Yon L - PLoS ONE (2014)

CgA levels in the plasma of patients with pheochromocytoma.(A) Scattergram of CgA concentrations in plasma samples of patients with pheochromocytoma before surgical removal of the tumor (preop, +, n = 37). (B) Distribution of CgA preoperative concentrations of patients reported in (A), depending on the adrenal (PHEO, ▴, n = 26) or extra-adrenal (PGL, ▾, n =  11) location of the tumor, the benign (•, n = 32) or malignant (▪, n = 5), and the sporadic (♦, n = 24) or hereditary (•, n = 13) nature of the neoplasms. The grey zone represents the cut-off level for the CgA test assay as indicated by the manufacturer. See legends of Figure 2 for other designations.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3921219&req=5

pone-0088698-g003: CgA levels in the plasma of patients with pheochromocytoma.(A) Scattergram of CgA concentrations in plasma samples of patients with pheochromocytoma before surgical removal of the tumor (preop, +, n = 37). (B) Distribution of CgA preoperative concentrations of patients reported in (A), depending on the adrenal (PHEO, ▴, n = 26) or extra-adrenal (PGL, ▾, n =  11) location of the tumor, the benign (•, n = 32) or malignant (▪, n = 5), and the sporadic (♦, n = 24) or hereditary (•, n = 13) nature of the neoplasms. The grey zone represents the cut-off level for the CgA test assay as indicated by the manufacturer. See legends of Figure 2 for other designations.
Mentions: Plasma concentrations of CgA in preoperative patients (n = 37) ranged from 6-780 U/l with a median value of 41 U/l (Figure 3A). CgA concentrations were not significantly different between patients with pheochromocytoma or paraganglioma [46.5 (7-770) vs 38 (6-780) U/l, respectively] (Figure 3B). Similarly, CgA levels were not significantly different between patients with benign or malignant neoplasms [39.5 (6-780) vs 58 (10-770) U/l, respectively] (Figure 3B). In contrast, CgA concentrations were significantly higher in patients with sporadic compared to hereditary tumors [55 (10-780) vs 23 (6-770) U/l, respectively] (p<0.05) (Figure 3B). A positive correlation was found between CgA and WE-14 concentrations in the plasma of patients with pheochromocytoma in which high plasma levels of CgA are associated with high levels of WE-14 (r  =  0.717, p<0.001, n = 37) (Figure 4). In addition, except for malignant pheochromocytomas, WE-14 levels were positively correlated to CgA levels in each group of patients (data not shown). No correlation was found between tumor size and CgA levels (r  =  0.339) (data not shown).

Bottom Line: Granins and their derived peptides are valuable circulating biological markers of neuroendocrine tumors.However, we found that WE-14 measurement improved the diagnostic sensitivity when combined with the results of CgA or EM66 assays.These findings support the notion that granin-processing products may represent complementary tools for the diagnosis of neuroendocrine tumors.

View Article: PubMed Central - PubMed

Affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), U982, Mont-Saint-Aignan, France ; Normandy University, Normandy, France ; Rouen University, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Institute for Research and Innovation in Biomedicine (IRIB), Mont-Saint-Aignan, France ; Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, Montreal, Quebec, Canada.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus