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.