Evaluation of chromogranin A determined by three different procedures in patients with benign diseases, neuroendocrine tumors and other malignancies

Abstract

CgA is not a specific tumormarker and abnormal concentrations may be found in non-NET´s. The higher AUC, sensitivity and specificity obtained with the ELISA and IRMA indicates that these are the best techniques to determine CgA.

Chromogranin A as circulating marker for diagnosis and management of neuroendocrine neoplasms: more flaws than fame

“…The most critical discrepancies were (a) the composition of the case groups, with the strongest difference being represented by the fact that some studies included NEN from all sites (Bernini et al 2001, Donica et al 2010, Molina et al 2011, Korse et al 2012, Marotta et al 2012, Tohmola et al 2014, whereas some others tried to analyze more homogeneous set of patients, mainly selecting gastroenteropancreatic tumors (Tomassetti et al 2001a, Peracchi et al 2003, Nehar et al 2004, Zatelli et al 2007, Belli et al 2009, Modlin et al 2013 (Table 1); (b) the composition of the control groups: although the majority of studies used healthy subjects as controls (Bernini et al 2001, Tomassetti et al 2001b, Peracchi et al 2003, Nehar et al 2004, Campana et al 2007, Zatelli et al 2007, Belli et al 2009, Donica et al 2010, Molina et al 2011, Korse et al 2012, which represents the best approach to assess the diagnostic performance of a marker (Shapiro 1999), some researchers determined the metrics of circulating CgA by comparing NEN with non-NEN tumors (Nobels et al 1998, Panzuto et al 2004 or active versus diseasefree NEN (Bajetta et al 1999, Panzuto et al 2004; (c) the consideration of interfering factors: some authors tried to clean up the control group from those conditions with known effect on CgA levels, thus obtaining a more pristine evaluation of marker specificity (Bernini et al 2001, Tomassetti et al 2001b, Nehar et al 2004, Campana et al 2007…”

“…The role of the reported non-oncological conditions in affecting specificity of circulating CgA as a diagnostic marker of NEN emerges when comparing ROC analyses of studies trying to skim non-neoplastic controls for the presence of possible false-positive inductors with those not performing any selection (Table 1). Indeed, authors applying the former approach reported values ranging from 95 to 100% (Bernini et al 2001, Tomassetti et al 2001b, Nehar et al 2004, Campana et al 2007, Belli et al 2009, Molina et al 2011, with the only exception of Zatelli et al (2007), who found 84/85% specificity (based on the detection method) likely due to the fact that CAG was not ruled out. By contrast, specificity was less than 90% in the majority of studies where exclusion of interfering conditions was not performed (Peracchi et al 2003, Donica et al 2010, Vezzosi et al 2011, Marotta et al 2012, Tohmola et al 2014.…”

“…By contrast, there are some tumors showing CgA elevation where the presence of histological neuroendocrine differentiation has not been reported, such as primary hepatocellular cancer (Spadaro et al 2005) and breast cancer (Giovanella et al 2001). To date, the capability of circulating CgA in discriminating NEN from other malignancies has been evaluated by many studies, which reported controversial results characterized by wide variation of specificity values (Nobels et al 1998, Nehar et al 2004, Panzuto et al 2004, Molina et al 2011, Marotta et al 2012 (Table 3). This was likely due to the heterogeneity of both NEN groups and neoplastic controls, with the latter including different tumor types.…”

The biochemical utility of chromogranin A, chromogranin B and cocaine- and amphetamine-regulated transcript for neuroendocrine neoplasia

“…73 Although the sensitivity and specificity of circulating CgA measurement in the biochemical diagnosis of NEN have been extensively studied, there has been less focus on CgB measurement and to date, there is one only published study on CART measurement. 46,73,82,88,[98][99][100][101][102] Table 3 summarizes the various studies which investigate the sensitivity and specificity of circulating CgA, CgB and CART measurement in NEN. There is considerable variation in the sensitivity of CgA measurement among the studies.…”

“…103,105,[108][109][110][111][112][113] When metastatic non-NEN CgA concentrations were compared with non-metastatic non-NEN CgA concentrations, no significant difference was found. 82 Although circulating CgA is elevated in some non-NEN tumours, it is unlikely that CgA is more sensitive than traditionally used biomarkers. For instance, CgA measurement was not as sensitive as the breast carcinoma biomarker cancer antigen (CA) 15.3 109 or the prostate biomarker prostate-specific antigen (PSA).…”