COSA:NETs guidelines/Biochemical markers
|Information on authorship and revision|
|Last reviewed:||November 2010|
|Author(s):||Michael Michael (Chair), Bruce Robinson, Peter Katelaris|
Neuroendocrine tumours frequently demonstrate elevation of one or more biochemical markers which may be used to follow the course of disease and response to therapy. Some of these markers may be associated with a syndrome due to hormone excess. Positive immunohistochemistry for a marker may not be associated with measurable hormonal overproduction and a syndrome. Hormone production may alter over the course of disease.
Commonly available markers are described. Consideration should be given to referring patients with functioning pancreatic NETs to an endocrinology service.
Serum Chromogranin A (CgA)
Serum Chromogranin A (CgA) is the most established NET marker for diagnosis and monitoring progression or treatment response.
CgA stabilises intracellular vesicles and regulates post-translational protein processing. It is elevated in between 60% and 100% of patients with NETs, including functioning and non-functioning midgut carcinoids, pancreatic islet tumours (functioning and non-functioning) and phaeochromocytomas. Specificity may be lower in midgut NETs. It is proportional to tumour size, and may be useful to estimate prognosis, monitor response to therapy and possibly for monitoring for progression. However the correlation may be lost during SSA therapy.
CgA is more reliable than Ur 5HIAA (urine 5-hydroxyindoleacetic acid) in terms of sensitivity and for detecting small recurrences in follow-up. False positives may result from decreased renal function, atrophic gastritis, liver function impairment, inflammatory bowel disease and proton pump inhibitor (PPI) therapy.
CgA should be used in combination with imaging to measure tumour bulk and response. It can be used for monitoring in the following circumstances:
- In patients with completely resected disease, for relapse. For example if CgA is trending upwards, (i.e. > 50% baseline outside normal range) and there are no likely causes of a false positive, further investigation should be conducted. Consider a CT scan and functional imaging with octreotide scan.
- In a patient who has had metastatic disease treated, for the evaluation of response or progression.
CgA is not a measure of tumour bulk for gastrinomas, therefore other hormonal markers need to be measured. It is also not a useful measure for patients on proton pump inhibitors.
Antibody-derived assays are variable and availability is limited to only a few centres. Patient samples should be measured in the same lab consistently. Given the potential inaccuracy of reports of high levels (with anecdotal reports of ±20% in same sample measured on two different occasions, but usual uncertainty of assay ±17%) the laboratory(s) should be asked for confidence intervals and interpatient variation in duplicate samples.
Chromogranin B (CgB)
This assay is not currently available in Australia and NZ (but can be done in the UK), and if available, is preferred to CgA in patients with renal and hepatic impairment.