Improved diagnostic accuracy for neuroendocrine neoplasms using two chromogranin A assays

Chromogranin A (Cg A) is the best available diagnostic marker for neuroendocrine neoplasms (NENs). However, clinical interpretation of Cg A results may be limited by considerable heterogeneity between commonly available Cg A assays. Variation in diagnostic accuracy of these assays largely reflects differences in antibody specificities. We compared the diagnostic utility of four Cg A assays [Imperial Supra-regional Assay Service radioimmunoassay (SAS) and three commercial assays, Cisbio, DAKO and Eurodiagnostica].

Plasma Cg A was measured using these four assays in 125 patients with NENs, 41 patients with cancers other than NENs and 108 healthy controls.

There was no significant difference in diagnostic accuracy between any of the four assays alone and no single assay positively identified all patients with NEN. However, concordance between assays was variable. Cisbio and SAS assays were least concordant. We, therefore, hypothesized that using a combination of the least concordant Cg A assays will improve NEN diagnosis by detecting a larger number of Cg A epitopes and hence patients with NEN. Consistent with our hypothesis, multiple logistic regression analysis showed that the combination of Cisbio and SAS assays was more useful than any other combinations or any assay alone in predicting a NEN diagnosis.

Although individually, all four Cg A assays are similarly useful for the measurement of Cg A in the diagnosis of a NEN, in patients with a suspected NEN, negative results by one assay should prompt analysis by a second assay. The combination of Cisbio and SAS assays may have greatest diagnostic utility.