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. Cancer 1999;86:858–65. © 1999 American Cancer Society.

Metastatic Carcinoid Tumors: A Clinical Review

“…In contrast to urinary 5-HIAA and platelet serotonin levels, it can be used in the detection of functioning as well as nonfunctioning tumors. Although its specificity is lower than that of urinary 5-HIAA level (86% and 100%, respectively), its sensitivity is much higher (35% and 68%, respectively) [34] and reported to be the highest in the foregut and functioning tumors. Levels of CgA are correlated with tumor burden [37], and a direct comparison between serum CgA and urinary 5-HIAA levels showed a higher accuracy for CgA in the detection of relapse in carcinoid patients [38].…”

“…The specificity of this determination is almost 100%, but the sensitivity is reported to be much lower (35%) [34]. Urinary 5-HIAA levels can be influenced by food (e.g., bananas, avocados, pineapple, and walnuts) consumption and medication use [35].…”

Circulating biomarkers in gastroenteropancreatic neuroendocrine tumours

“…In patients with poorly differentiated NETs NSE might be elevated despite normal CgA. Increased levels of NSE are also roughly correlated with tumour size, although the specificity is lower than that of CgA (Baudin et al 1998, Bajetta et al 1999, O'Toole et al 2009, Vinik et al 2009). The combination of CgA and NSE has a higher sensitivity than either parameter separately (Oberg & Stridsberg 2002).…”

Significance of plasma chromogranin A determination in neuroendocrine tumour (NET) diagnosis.

“…Recent studies confirmed that the measurement of CgA levels in blood can also be used to diagnose and to monitor neuroendocrine tumours during treatment [6,10,14,[16][17][18].…”

“…The neuroendocine cells can be found in: adrenal medulla, sympathetic nerves endings, cerebral cortex, pituitary gland, gastrointestinal tract, thyroid, parathyroid glands, pancreatic islets and lungs [2,4,8,10]. The synthesis and secretion of CgA may be intensified in the neuroendocrine tumour (NET) cells [4,9,14,15].…”