Chromogranin A, neuron specific enolase, carcinoembryonic antigen, and hydroxyindole acetic acid evaluation in patients with neuroendocrine tumors

Abstract

Background: Chromogranin A (CgA), neuron specific enolase (NSE), carcinoembryonic antigen (CEA), and urinary 5-hydroxyindole-3-acetic acid (5-HIAA) are the markers currently used in the diagnosis, prognosis, and follow-up of patients with neuroendocrine tumors (NETs). The authors examined the role of such biomarkers in a large series of patients with NETs.

Methods: One hundred and twenty-seven patients entered the study. Multiple blood and 24-hour urine specimens were assayed for biomarker quantitation.

Results: The accuracy of each marker was assessed in patients with (n = 106) and without (n = 21) disease. CgA proved to be the best marker (specificity of 85.7% and sensitivity of 67.9%). Patients with disease had significantly higher CgA and NSE levels compared with disease free patients (P = 0.00003 and P = 0.00240, respectively). NSE and 5-HIAA determination showed a very high specificity (100%) but a rather low sensitivity (32.9% and 35.1%, respectively). CEA was found to have little diagnostic value (sensitivity of 15.4%). CgA was the most sensitive marker for detecting patients with disseminated disease and 5-HIAA displayed the highest sensitivity in identifying syndromic patients. Tumor marker modifications were studied during follow-up. In particular, rises in CgA were associated with progressive disease in 83.3% of cases and stable CgA was associated with stable disease in 53.8% of cases. The relation between CgA modifications and liver lesions during follow-up also was studied; increases in CgA levels were associated with local progression in 100% of cases and stable marker levels were found in 68.7% of the patients with unchanged lesions.

Conclusions: The results of the current study demonstrate that CgA has the highest accuracy and is the most reliable biomarker reflecting the clinical evolution of NETs.