Chromogranin A in diagnosing and monitoring patients with gastro-entero-pancreatic 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 work-up and follow-up of gastro-entero-pancreatic neuroendocrine neoplasms (GEP-NENs). Herein, we assessed the clinical utility of CgA in diagnosing and monitoring a large series of GEP-NENs. Patients and Methods: 181 GEP-NEN patients (87 males, 94 females), with pancreatic (81) and gastrointestinal (100) neoplasm, were included. 99 patients were G1 (Ki-67 ≤2%) NENs, 57 G2 (Ki-67 3-20%), 25 G3 (Ki-67 >20%). 81 patients were at TNM stage I, 14 at II, 17 at III, 69 at IV. 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 non-functioning tumors (295 vs. 43 U/l, p = 0.0001) and in patients with metastases than without (324.5 vs. 42 U/l, p = 0.0001). At logistic regression analysis the baseline CgA levels were significantly associated with the Ki-67 index (p < 0.0001) and the 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 was 74% and 64.5%, respectively. The low Ki-67 index, the type of treatment and the 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 carries a significant prognostic meaning.