The Pathology Dictionary Team
May 10, 2023

What is chromogranin?

Chromogranin is a type of protein found primarily in neuroendocrine cells. There are three chromogranin proteins encoded by the CHGA (chromogranin A), CHGB (chromogranin B), and CHGC (chromogranin C) genes.

What does chromogranin do?

Chromogranins play important roles in the regulated secretion of hormones and specialized proteins called neuropeptides. They are present in small intracellular structures called secretory vesicles and are released along with other bioactive substances during a process called exocytosis. Chromogranin A has been identified as a prohormone that can be processed into various biologically active peptides, including vasostatin, pancreastatin, and chromostatin.

In addition to their role in secretory granules, chromogranins have been implicated in other cellular functions, such as calcium binding, protein trafficking, and modulation of immune responses. They are also known to be involved in the pathogenesis of certain diseases, including neuroendocrine tumors, cardiovascular disorders, and autoimmune diseases.

Why do doctors test for chromogranin?

The measurement of chromogranin A levels in the blood is often used as a diagnostic and prognostic marker for neuroendocrine tumors, such as carcinoid tumors and neuroblastomas. Elevated levels of chromogranin A can indicate the presence of these tumors or be used to monitor treatment response. Pathologists use a test called immunohistochemistry (IHC) to look for cells expressing chromogranin in a tissue sample.

Chromogranin. This picture shows a neuroendocrine tumour made up of cells that express chromogranin. The chromogranin-expressing cells are brown.

What types of cells normally express chromogranin?

Chromogranin expression is predominantly found in neuroendocrine cells, which are specialized cells that release hormones and neurotransmitters. These cells are distributed throughout the body.

Normal cells that express chromogranin include:

  • Neuroendocrine cells in the gastrointestinal tract: Chromogranin is expressed in enterochromaffin cells of the stomach, small intestine, and large intestine. These cells secrete various hormones and peptides, including serotonin, gastrin, and somatostatin.
  • Pancreatic islet cells: Chromogranin is expressed by islet cells of the pancreas, particularly in the beta cells that produce insulin. It is involved in the packaging and secretion of insulin along with other hormones like glucagon.
  • Adrenal medulla: Chromogranin is expressed in the chromaffin cells of the adrenal medulla. These cells release catecholamines, such as epinephrine and norepinephrine, as part of the body’s stress response.
  • Pituitary gland: Chromogranin is found in various cell types within the pituitary gland, including corticotrophs, somatotrophs, and lactotrophs. These cells produce hormones like adrenocorticotropic hormone (ACTH), growth hormone (GH), and prolactin.
  • Thyroid C cells: Chromogranin is expressed by parafollicular cells, also known as C cells, of the thyroid gland. These cells produce calcitonin, a hormone involved in calcium regulation.

What types of tumours express chromogranin?

Chromogranin expression is frequently observed in tumours made up of neuroendocrine cells. These types of tumours include carcinoid tumours, well differentiated neuroendocrine tumours, poorly differentiated neuroendocrine carcinomas, small cell carcinomas, large cell neuroendocrine carcinomas, medullary thyroid carcinomas, Merkel cell carcinoma, pheochromocytomas, and paragangliomas. Chromogranin can also be expressed by other types of tumours if the cells in the tumour have started to change into neuroendocrine cells. Pathologists often describe this as neuroendocrine differentiation.

What does positive for chromogranin mean?

Positive means that the cells in the tissue sample were making chromogranin protein.

What does negative for chromogranin mean?

Negative means that the cells in the tissue sample were not making chromogranin.

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