From the Guidelines
Tumor markers for secretory neuroendocrine tumors (NETs) primarily include chromogranin A (CgA), pancreatic polypeptide (PP), and specific hormones depending on the tumor type, as well as 5-hydroxyindoleacetic acid (5-HIAA) for serotonin-secreting tumors. According to the guidelines for the management of gastroenteropancreatic neuroendocrine tumors 1, CgA is the only general marker for NETs, usually found in high concentrations regardless of whether the tumor is accompanied by hormone-related clinical features. However, chromogranin B (CgB) may be elevated when CgA is in the reference range.
Key Tumor Markers
- Chromogranin A (CgA): elevated in most NETs, but can be falsely elevated by proton pump inhibitors or renal failure 1
- Pancreatic polypeptide (PP): useful additional or alternative general marker, particularly when CgA or CgB are within the reference range 1
- 5-hydroxyindoleacetic acid (5-HIAA): useful for serotonin-secreting tumors, with levels above a certain threshold suggesting a NET 1
Tumor-Specific Markers
- Insulin and C-peptide for insulinomas: measurement of C peptide or pro-insulin is helpful, and a 48-72 h fast under hospital supervision with serial blood glucose analysis is the gold standard diagnostic tool 1
- Gastrin for gastrinomas: diagnosis may be difficult due to elevated gastrin levels in common conditions, and secretin stimulation and intragastric pH may be needed in some cases 1
- Other specific hormones: depending on clinical presentation, such as glucagon for glucagonomas, and vasoactive intestinal peptide (VIP) for VIPomas
Interpretation and Clinical Context
These markers are valuable not only for diagnosis but also for monitoring treatment response and disease recurrence, with serial measurements providing insight into disease progression or regression 1. However, interpretation should always consider clinical context, as no single marker is perfectly sensitive or specific for NETs.
From the Research
Tumor Markers for Secretory Neuroendocrine (NE) Tumors
- Chromogranin A (CgA) is a widely used marker for neuroendocrine tumors, as it is co-released with peptide hormones and its serum concentration can be used as a marker of neuroendocrine activity 2, 3, 4, 5
- CgA is elevated in patients with various neuroendocrine tumors, including carcinoids and phaeochromocytomas, and its levels are strongly correlated with tumor volume 2, 6
- Other chromogranins, such as chromogranin B (secretogranin I) and chromogranin C (secretogranin II), can also be used as markers, but their sensitivity and specificity are lower than CgA 6
- Pancreastatin, a fragment of CgA, can also be used as a marker, but its levels are not as reliable as CgA 6
- Neuron-specific enolase (NSE) is another marker that can be used, but its diagnostic usefulness is lower than CgA 4
Clinical Utility of Chromogranin A
- CgA can be used as a serum marker for neuroendocrine tumors, especially for those with no specific peptide marker available 2, 5
- CgA levels can be used to monitor tumor growth and response to treatment 2, 6, 5
- However, CgA has limitations, including non-specificity and potential false-positive results due to other pathological processes 3