INSM1

INSM1 stands for insulinoma-associated protein 1. It is a protein found inside certain types of cells in the body, especially neuroendocrine cells. These are specialized cells that receive signals from the nervous system and release hormones in response. INSM1 plays a key role during development and helps guide immature cells to become fully functional neuroendocrine cells. Because of its strong and specific expression in neuroendocrine cells, pathologists use INSM1 as a marker to help identify neuroendocrine tumours.

What types of normal cells and tissues express INSM1?

INSM1 is mainly found in the nucleus of neuroendocrine cells throughout the body.

These cells are present in many organs, including:

• The lungs.

• The gastrointestinal tract (stomach, intestines, pancreas).

• The thyroid gland.

• The adrenal glands.

• The parathyroid glands.

• Parts of the brain and spinal cord.

INSM1 is typically active during early stages of development but can also be found in mature neuroendocrine tissues and tumours.

How do pathologists test for INSM1?

Pathologists test for INSM1 using a method called immunohistochemistry (IHC). A small sample of tissue is treated with special antibodies that attach to the INSM1 protein. If the protein is present, a visible colour change appears in the nucleus of the cells under the microscope. A positive result means the cells express INSM1, while a negative result means they do not.

INSM1 testing is especially useful when a tumour may be of neuroendocrine origin. It is often used alongside other neuroendocrine markers such as synaptophysin, chromogranin A, and CD56 to confirm the diagnosis.

What types of tumours express INSM1?

INSM1 is strongly expressed in many neuroendocrine tumours, including:

• Well-differentiated neuroendocrine tumours (carcinoid tumours) – These tumours are commonly found in the lungs, gastrointestinal tract, or pancreas.

• Small cell neuroendocrine carcinoma – A highly aggressive cancer that can arise anywhere in the body but is commonly found in the lungs.

• Large cell neuroendocrine carcinoma – Another highly aggressive cancer that is commonly found in the lungs.

• Medullary thyroid carcinoma – A neuroendocrine cancer of the thyroid gland.

• Merkel cell carcinoma – A rare skin cancer with neuroendocrine features.

• Paraganglioma and pheochromocytoma – Tumours of the adrenal glands or other neuroendocrine tissues.

• Neuroblastoma and ganglioneuroblastoma – Childhood cancers of the nervous system.

INSM1 is also useful in identifying tumours that have neuroendocrine differentiation, even if they do not appear typical under the microscope. It is especially valuable when other neuroendocrine markers like synaptophysin or chromogranin are negative or only weakly positive.

Why is INSM1 important in a pathology report?

INSM1 is important because it helps pathologists determine whether a tumour is a neuroendocrine tumour. Knowing whether a tumour has neuroendocrine features is critical for:

• Making an accurate diagnosis.

• Choosing the most appropriate treatment.

• Predicting how the tumour might behave over time.

INSM1 is considered a sensitive and specific marker, meaning it is very reliable for identifying neuroendocrine tumours. It has largely replaced older markers in some settings and is now commonly included in panels used to diagnose these cancers.

Questions to ask your doctor

• Does this confirm that my tumour is a neuroendocrine tumour?

• Were other neuroendocrine markers like synaptophysin or chromogranin A also tested?

• How does INSM1 help guide my treatment plan?

• Do I need additional tests to better understand my tumour type?