Chromogranin A in gastric neuroendocrine tumours: an immunohistochemical and biochemical study with region-specific antibodies

Abstract

The aim of the present study was to investigate ECLomas and enterochromaffin-like (ECL) cell hyperplasia in gastric human mucosa regarding the immunohistochemical expression of chromogranin A (CgA) epitopes and to measure the same CgA epitopes in plasma samples. Eight gastric biopsies from ECLomas, seven of type I and one of type III, and biopsies from one patient showing only ECL cell hyperplasia were included in the study. Our results revealed a varying expression of region-specific CgA epitopes in the ECLomas regarding both the frequency of immunoreactive cells and intensity of immunoreactivity. CgA284-301 (pancreastatin) was not revealed in any neoplasm, whereas CgA361-372 (catestatin) was expressed in all ECLomas. However, the number of immunoreactive cells to vesicular monoamino transporter 2 (VMAT 2) or the commercial monoclonal CgA (CgA250-284) antibodies were generally higher. The plasma concentrations of the region-specific CgA radioimmunoassays differed considerably, with highest concentrations of CgA1-17 and CgA116-130 epitopes and the lowest with the CgA17-37, CgA63-76, CgA238-247 and CgA441-424 epitopes. No relationship was found between tissue expression and plasma concentration of CgA epitopes. In conclusion, this study shows that VMAT 2 and the commercial CgA antibodies seem more useful for histopathological diagnosis of ECLomas than the antibodies to the other CgA regions.

The endocrine role for chromogranin A: A prohormone for peptides with regulatory properties

“…Thus, in view of the complex patterns of vasostatin effects on the heart and vascular endothelium (see Cardiovscular processes below), the causal relationship between lack of CgA and hypertension may be more complex than so far suggested from the effects of exogenous catestatin. [53][54][55][56][57][58][59][60][61][62][63][64][65][66] ), in accordance with our previous report [54]. Highly different effects have been assigned to these three domains, suggesting structure-function relationships.…”

“…Moreover, a helical wheel prediction suggested an amphipathic a-helix for the calmodulin (CaM)-binding synthetic peptide CgA 40-65 [110]. In accordance with the potent antifungal activity of CgA [47][48][49][50][51][52][53][54][55][56][57][58][59][60][61][62][63][64][65][66] , this peptide has been named chromofungin [54]. As reviewed above, this peptide also inhibits myocardial inotropy in the frog [43] and the intracellular rise in calcium in the pressureautoregulating rat posterior cerebral artery [98].…”

“…A performance assessment of three commercial kits for circulating human CgA [59] indicates significantly different properties and specificities of the antibodies [47,[58][59][60][61], a factor that should be taken into consideration when comparing results from different clinical studies of plasma and serum CgA. In normal human plasma CgA ranges from 0.5 nM [62], 2 nM [63,64] and 5 nM [59,65,66], reflecting the specificities of the antibodies used for the RIAs, still lower than the value of 7 nM for CgA in bovine serum [67]. A similar range (1-6 nM) has been reported for CgA in mammals using antisera to selected, highly conserved CgA domains, such as VS-I, betagranin, catestatin and the near-terminal peptide GE-25 [10,67,68].…”

“…CgA [47][48][49][50][51][52][53][54][55][56][57][58][59][60][61][62][63][64][65][66] The C-terminal region of VS-I, unique in several aspects, is cationic, hydrophobic and contains the third amphipathic a-helix CgA 53-66 (Fig. 2).…”

Processing-Independent Quantitation of Chromogranin A in Plasma from Patients with Neuroendocrine Tumors and Small-Cell Lung Carcinomas

“…Measurements are performed with antisera raised against purified full-length CgA or large fragments from tumor patients (3, 23, 29 -36 ), or with sequence-specific RIAs (15,32,(37)(38)(39). Highly variable diagnostic sensitivities occur depending on tumor type and specificity of the assay employed.…”