Chromogranin A in Diagnosing and Monitoring Patients with Gastroenteropancreatic Neuroendocrine Neoplasms: A Large Series from a Single Institution

Background/Aims: Plasma chromogranin A (CgA) is the most widely used biochemical biomarker in the diagnostic workup and follow-up of gastroenteropancreatic neuroendo- crine neoplasms (GEP-NENs). Herein, we assessed the clinical utility of CgA in diagnosing and monitoring a large series of GEP-NENs. Patients and Methods: A total of 181 GEP-NEN patients (87 males, 94 females) with pancreatic (n = 81) and gastrointestinal neoplasms (n = 100) were included; 99 patients had grade (G)1 NENs (Ki-67 ≤2%), 57 G2 NENs (Ki-67 3-20%) and 25 G3 NENs (Ki-67 >20%); 81 patients had tumor-node-metastasis (TNM) stage I, 14 stage II, 17 stage III and 69 stage IV cancer. For every patient, CgA values were assessed at diagnosis and during follow-up. Results: At diagnosis, the CgA values were above the upper reference limit in 148 patients (82%); the median CgA levels were significantly higher in functioning than in nonfunctioning tumors (295 vs. 43 U/l; p = 0.0001) as well as significantly higher in patients with metastases than in those without metastases (324.5 vs. 42 U/l; p = 0.0001). In logistic regression analysis, baseline CgA levels were significantly associated with Ki-67 index (p < 0.0001) and TNM stage (p < 0.0001) independently of the age and sex of the patient and the primary site of the tumor. The overall 5- and 10-year survival rates were 74 and 64.5%, respectively. A low Ki-67 index, the type of treatment and an early CgA decrease after treatment were positively correlated with the survival rate. After radical surgery, 15/95 patients relapsed, and an increase in CgA values anticipated the clinical and objective disease recurrence after a period of 9-12 months. Conclusions: In GEP-NENs, plasma CgA has a significant prognostic relevance.