INI1 (SMARCB1): Definition

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INI1 is a protein found in the nucleus of every normal cell in the body. It is made by a gene called SMARCB1, and you may see either name in your report. Some laboratories write INI1, some write SMARCB1, and a few write BAF47. All three refer to the same thing.

INI1 is a tumor suppressor, which means its normal job is to help stop cells from growing when they should not. It works by controlling how tightly the DNA is packed, which determines which genes a cell can read.

Why is the INI1 result the opposite of most stains?

This is the most important thing to understand about an INI1 result, and it catches many people out.

For most stains used in pathology, a positive result identifies something and a negative result means nothing was found. INI1 works the other way round. Every normal cell makes INI1, so normal tissue stains positive. A negative INI1 result is abnormal. It means the tumor cells have lost the protein, and that loss is what defines a specific group of tumors.

Reports describe this in several ways, all meaning the same thing: loss of INI1 expression, INI1 negative, INI1 deficient, or loss of nuclear staining. The report will often note that normal cells in the same sample stained positive, which confirms the test worked properly. Those normal cells act as a built-in control.

How is INI1 tested?

INI1 is detected using immunohistochemistry, a test that uses antibodies to find a specific protein in a tissue sample. Where INI1 is present, the nuclei take up a colored stain that the pathologist can see under the microscope.

When the stain shows loss, the SMARCB1 gene is often tested as well, usually by next-generation sequencing or a test that looks for missing pieces of a chromosome. This confirms the finding and shows how the gene was lost, which matters for the inheritance question discussed below.

Which tumors show loss of INI1?

Loss of INI1 defines a group of tumors that occur mainly, though not only, in children and young adults. Finding the loss can change a diagnosis entirely.

Rhabdoid tumors. Including the rhabdoid tumor of the kidney, rhabdoid tumor of the liver, and rhabdoid tumors elsewhere in the body. These occur mainly in infants and young children.
Atypical teratoid/rhabdoid tumor. The equivalent tumor arising in the brain, usually in children under 3.
Epithelioid sarcoma. A soft tissue cancer seen mainly in adolescents and young adults.
Poorly differentiated chordoma. An uncommon form of a bone tumor of the spine and skull base, seen in younger patients.
Some other tumors. Including renal medullary carcinoma and certain myoepithelial tumors.

Why the result can change a diagnosis

Several childhood tumors look similar under the microscope, and INI1 is often the test that separates them. The clearest example is in the liver. A hepatoblastoma containing a pattern called small cell undifferentiated looks much like a rhabdoid tumor of the liver. If INI1 is retained, the diagnosis stands as hepatoblastoma. If INI1 is lost, the tumor is a rhabdoid tumor, which is a different disease with a different treatment plan.

A similar situation arises in the brain and in soft tissue, where INI1 separates rhabdoid tumors from other tumors made of small round cells. This is why the stain is performed even when the diagnosis seems settled.

Does loss of INI1 mean an inherited condition?

Sometimes, which is why the result matters beyond the person with the tumor.

In most people, the SMARCB1 gene is lost only within the tumor cells and nowhere else in the body. In a meaningful minority, particularly infants and young children with rhabdoid tumors, one non-working copy of the gene is present in every cell from birth. This is called rhabdoid tumor predisposition syndrome, and it can be passed through a family.

For this reason, genetic testing on a blood or saliva sample is generally recommended for anyone diagnosed with a rhabdoid tumor. This applies regardless of age and whether anyone else in the family has been affected. That test looks at the DNA a person was born with, rather than at the tumor. A positive result has implications for brothers and sisters, for future children, and for the choice of donor if a stem cell transplant is ever considered. You can read more in our article What is a hereditary cancer syndrome?

Questions to ask your doctor

Was an INI1 or SMARCB1 stain performed on my tissue sample?
Was the protein retained, which is normal, or lost, which is abnormal?
Did normal cells in the sample stain positive, confirming the test worked?
How does this result change or confirm the diagnosis?
Was the SMARCB1 gene itself tested as well, and what did that show?
Should genetic testing on blood or saliva be done to check whether this change was present from birth?
If so, what does that mean for my other children or my relatives?
Does this result change the treatment plan?