Clinical significance of blood chromogranin A measurement in neuroendocrine tumours.
BACKGROUND
Tumour marker measurement gives clinicians useful information for the follow-up and management of patients with neuroendocrine tumours (NETs). The currently used tumour markers for NETs are neuron-specific enolase (NSE) and chromogranin A (CgA). The clinical accuracy of these biomarkers depends on histotype and disease extent. CgA is thought to be the optimal marker for most NETs, as it is independent of the biological characteristics of the tumour.


OBJECTIVE
In this study we investigated the value of CgA assessment with respect to the other biomarkers in the diagnosis and follow-up of patients with different types of NETs. PATIENTS AIND METHODS: We measured CgA, NSE, carcinoembryonic antigen (CEA) and urine 5-hydroxy-3-indoleacetic acid (5-HIAA) in 290 patients with 127 gastroenteropancreatic (GEP) tumours, 49 neuroblastomas, 36 lung tumours, 24 medullary thyroid carcinomas (MTCs). 15 pNETs, 12 paragangliomas. 7 Merkel's cell carcinomas (MCCs) and 20 NETs of unknown origin. CgA and 5-HIAA were quantitated by immunoenzymatic assays, while NSE and CEA were determined by radioimmunoassays.


RESULTS
The biomarkers' specificity in GEP tumours was 86% for CgA, 100% for NSE, 91% for CEA and 100% for 5-HIAA. The corresponding sensitivity was 68% for CgA, 33% for NSE, 15.4% for CEA and 35% for 5-HIAA. The sensitivity of CgA largely depends on disease extent or presence of functioning tumours and is highest in metastatic and syndromic patients. CgA determination in GEP tumour monitoring is useful to evaluate the response to therapy and to follow up patients with liver metastases. In neuroblastomas the overall specificity of NSE and CgA was 50%, and 83%, respectively. In these tumours NSE sensitivity was close to 90% in all clinical stages, while the sensitivity of CgA depended on clinical stage (50% for stage I and II, 60% for stage III and 100% for stage IV tumours). Also in this type of tumour changes in CgA levels correlated with objective response. In paragangliomas CgA measurement may provide useful clinical information. Measurement of CgA is of use in the diagnosis of lung carcinoids, while its value in MTCs, pNETs and MCCs is very limited.


CONCLUSIONS
CgA was confirmed to be the best tumour marker currently available for identifying patients suffering from NETs of the GEP system, lung carcinoids and neuroblastomas. CgA evaluation is recommended in the follow-up of patients with such tumours.
Seregni
E
E
Nuclear Medicine Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy.
Ferrari
L
L
Bajetta
E
E
Martinetti
A
A
Bombardieri
E
E
D014408:Biomarkers, Tumor / Q000032:analysis*; D002276:Carcinoid Tumor / Q000175:diagnosis / Q000473:pathology; D053379:Chromogranin A; D002864:Chromogranins / Q000032:analysis*; D003937:Diagnosis, Differential; D006801:Humans; D007118:Immunoassay; D008175:Lung Neoplasms / Q000175:diagnosis / Q000473:pathology; D009367:Neoplasm Staging / Q000379:methods*; D009447:Neuroblastoma / Q000175:diagnosis / Q000473:pathology; D018358:Neuroendocrine Tumors / Q000175:diagnosis* / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000175:diagnosis / Q000473:pathology; D011379:Prognosis; D012680:Sensitivity and Specificity; D013274:Stomach Neoplasms / Q000175:diagnosis / Q000473:pathology
D014408:Biomarkers, Tumor; C506150:CHGA protein, human; D053379:Chromogranin A; D002864:Chromogranins