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Cancer. 1999 Sep 1;86(5):858-65.

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

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  • 1Medical Oncology B Division, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy.



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.


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


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.


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.

Copyright 1999 American Cancer Society.

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