Chromogranin a as serum marker for gastroenteropancreatic neuroendocrine tumors: a single center experience and literature review

Abstract

The aim of this study was to assess the clinical sensitivities of the tumor markers chromogranin A (CgA), urinary 5-hydroxyindoleacetic acid (5-HIAA) and alkaline phosphatase (AP) in neuroendocrine tumors (NETs) of the GastroEnteroPancreatic-(GEP-) system depending on tumor primary location and metastatic spread. In a retrospective single-center series, sensitivities were evaluated in serum samples from 110 patients with midgut (n = 62) and pancreatic (n = 48) NETs. CgA levels were analyzed by a commercially-available immunoradiometric assay (CIS-bio) during routine follow-up in the years 2000-2009. CgA showed a higher sensitivity for midgut (68%) than pancreatic (54%) NETs. A higher CgA sensitivity and significantly higher median CgA values were found in patients with liver metastases than in those without, and in patients with hepatic and additionally extra-hepatic metastases than in those with hepatic and nodal metastases alone, respectively. We found an overall sensitivity for elevated 5HIAA excretion of 69% for midgut NETs and a significant correlation between median CgA and 5-HIAA values. The sensitivity of AP and the correlations of AP/CgA-data-pairs were low in both midgut and pancreatic NETs, although highest for metastatic pancreatic NETs. The sensitivity of CgA measurement depends on the NET primary location and spread of disease. 5-HIAA and CgA showed comparable sensitivity in midgut NETs, while AP does not seem to be useful as a tumor marker in GEP-NETs.

Figure 1

Box plots of median serum CgA levels (CgA in ng/mL) for the investigated 110 pancreatic and midgut NET patients, subdivided into patients without and patients with liver metastases, patients with liver (and lymph node) metastases only and patients with hepatic and additional extra-hepatic metastatic spread; n = number of patients.

Figure 2

Log₁₀-transformed median serum CgA levels [log10(CgA), CgA in ng/mL] of the whole study population (n = 110), pancreatic NET patients (n = 48) and midgut NET patients (n = 62), subdivided into patients without liver metastases and patients with liver metastases. n = number of patients.