Chromogranin A as a Marker for Diagnosis, Treatment, and Survival in Patients With Gastroenteropancreatic Neuroendocrine Neoplasm

Chromogranin A (CgA) not only plays an important role in pathologic diagnosis, but is also used as a circulating biomarker in patients with gastroenteropancreatic neuroendocrine neoplasm (GEP-NEN). However, the relationship between immunohistochemistry (IHC) expression and serum levels of CgA has not been investigated. The value of CgA for evaluating treatment response and prognosis is still not well understood. We conducted this study to assess the significance of CgA in GEP-NEN in terms of diagnosis, curative effects evaluation and prognosis. One hundred forty-five patients comprising 88 patients with active disease and 57 disease-free patients were enrolled in this study from January 2011 to November 2013. The expression of CgA was assessed by IHC, and serial serum CgA levels were measured by enzyme linked immunosorbent assay. The overall expression rate of CgA was 69.0% (100/145). CgA expression was associated with tumor site and stage (P < 0.05), but not correlated with prognosis (P = 0.07). Serum CgA levels were significantly higher in GEP-NEN patients with active disease when compared with disease-free patients (P = 0.001) or healthy participants (P < 0.001). A CgA cutoff value of 95 ng/ml discriminated between healthy subjects or disease-free patients and patients with active disease (sensitivity 51.2% and specificity 87.5%, respectively). There was a correlation between the CgA IHC expression and high serum CgA levels (R = 0.320, P = 0.002). Serum CgA levels were much higher in patients who classified as neuroendocrine carcinoma, mixed adenoendocrine carcinoma (P = 0.035) and who were on stage IV (P = 0.041). Changes in CgA levels normalization or ≥ 30% decrease suggested that patients had tumor response. Furthermore, patients with serum CgA levels higher than 95 ng/ml had a significantly shorter survival compared with patients with levels lower than 95 ng/ml (P < 0.001). CgA is a reliable pathologic and circulating maker for diagnosis of GEP-NEN. We further confirmed that serial measurement of CgA may be useful for evaluating the efficacy of different kinds of therapies in patients during follow-up, and serum CgA level ≥ 95 ng/ml may serve as a predictor of overall survial.