Immunohistochemical and Biochemical Studies with Region-Specific Antibodies to Chromogranins A and B and Secretogranins II and III in Neuroendocrine Tumors

Abstract

This short review deals with our investigations in neuroendocrine tumors (NETs) with antibodies against defined epitopes of chromogranins (Cgs) A and B and secretogranins (Sgs) II and III. The immunohistochemical expression of different epitopes of the granin family of proteins varies in NE cells in normal human endocrine and non-endocrine organs and in NETs, suggesting post-translational processing. In most NETs one or more epitopes of the granins were lacking, but variations in the expression pattern occurred both in benign and malignant NETs. A few epitopes displayed patterns that may be valuable in differentiating between benign and malignant NET types, e.g., well-differentiated NET types expressed more CgA epitopes than the poorly differentiated ones and C-terminal secretoneurin visualized a cell type related to malignancy in pheochromocytomas. Plasma concentrations of different epitopes of CgA and CgB varied. In patients suffering from carcinoid tumors or endocrine pancreatic tumors the highest concentrations were found with epitopes from the mid-portion of CgA. For CgB the highest plasma concentrations were recorded for the epitope 439-451. Measurements of SgII showed that patients with endocrine pancreatic tumors had higher concentrations than patients with carcinoid tumors or pheochromocytomas. SgIII was not detectable in patients with NETs.

Utility of chromogranin B compared with chromogranin A as a biomarker in Japanese patients with pancreatic neuroendocrine tumors

“…Many reports have indicated that CgB is different from CgA in its level/mode of expression (30). In the present study, the correlation between serum CgB and CgA was not high, probably reflecting the difference in expression mechanisms between CgB and CgA.…”

Improved diagnostic accuracy for neuroendocrine neoplasms using two chromogranin A assays

“…Cg A was measured in these samples and in 125 patient with NEN samples using the Imperial Supra‐regional Assay Service radioimmunoassay (SAS) and three different commercial assays (Cisbio, DAKO, Eurodiagnostica). Samples were processed and analysed following manufacturer’s recommendations for each kit 9–11 …”

“…Samples were processed and analysed following manufacturer's recommendations for each kit. [9][10][11]…”

“…The diagnostic accuracy of an assay depends upon antibody specificity and the molecular forms it recognizes. An assay that recognizes more forms is likely to have better diagnostic accuracy 10 . Although several commercial Cg A assays are currently available, the forms of Cg A detected by these assays vary owing to differences in antibody specificities and assay design.…”

“…An assay that recognizes more forms is likely to have better diagnostic accuracy. 10 Although several commercial Cg A assays are currently available, the forms of Cg A detected by these assays vary owing to differences in antibody specificities and assay design. This makes direct comparison between assays problematic.…”