The precise biological function of elevated chromogranin A (CgA) in neuroendocrine and nonneuroendocrine neoplasms remains unclear. Limited studies in cell and animal models have provided contradictory evidence as to whether CgA promotes or inhibits tumorigenesis. In a neuroendocrine tumor (NET)-derived cell line a study demonstrated that cyclooxygenase-2 (Cox-2) up-regulates both CgA expression and bioactivity with implications of this polypeptide in neuroendocrine cancer.
In our study, we indirectly tested the link between Cox-2 and CgA in a lot of 15 patients clinically suspected of pheochromocytoma by comparison with a lot of 15 matched controls without endocrine dysfunction. Biochemical diagnosis of pheochromocytoma was realized by differentially Elisa assay of plasma free normetanephrines (NMNp) /free metanephrines (MNp) and by plasma Elisa assay of CgA. Plasma Cox-2 was assayed by an Elisa research kit. All four parameters were assayed both in tumoral and normal subjects.We calculated means and standard errors in pheo group vs control subjects and we established statistically significant differences between all parameters assayed. Multiple regression showed important correlation coefficients between: NMNp/CgA: 0.86; NMNp/MNp:0.70; CgA/Cox-2:0.56. Practically,we proved the traffic control of the noradrenergic metabolite NMNp by CgA and Cox-2.Using Relative Operating Curve Analysis (ROC) we compared sensitivity and specificity of all four assayed parameters. Cox-2,CgA,NMNp proved the best sensitivity and a great specificity.
We can conclude that Cox-2 could be used as a prediction marker in pheochromocytoma pathology together with CgA/NMNp/MNp.
1-Cox-2 promotes CgA expression and bioactivity:evidence for a Prostaglandin E2 dependent mechanism and bioactivity:evidence for a Prostaglandin E2 dependent mechanism and the involvement of a proximal cyclic Adenosine 5'-Monophosphate-Responsive Element-Endocrinology 148(9):4310-4317,2007 - Connolly R et al.
2-Increased expression of cyclooxygenase-2 in malignant pheochromocytomas-J Clin Endocrinol Metab 86:5615-5619-2001- Salmenkiwi K. et al.
3-Pheochromocytoma-Lancet 366:665-675-2005 -Lenders JWM et al.