RB1: Definition

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RB1 is a gene that helps control when cells divide. It makes a protein called Rb (retinoblastoma protein). RB1 is a tumor suppressor gene, which means it normally acts as a brake on cell growth. When both copies of the gene stop working, cells can divide without control.

RB1 is named after retinoblastoma, a rare eye cancer in children, where researchers first discovered changes in this gene. Changes in RB1 are also found in several other tumors. This article explains what RB1 does, how pathologists test it, and what the results in your pathology report mean.

What does RB1 do?

Before a cell divides, it passes through a series of checkpoints. The Rb protein guards one of the most important checkpoints. It blocks the cell from copying its genetic material and dividing until it receives the right signals.

Every cell has two copies of RB1, one inherited from each parent. As long as one copy works, the brake usually holds. When both copies are lost or damaged, the brake is removed, and the cell can divide when it should not.

What is the difference between an inherited and an acquired RB1 change?

RB1 changes can be present from birth or develop later in life:

Inherited (germline) changes. Some people are born with a change in one copy of RB1 in every cell of the body. They have a high chance of developing retinoblastoma in early childhood, often in both eyes. They also have a higher chance of developing other cancers later in life, such as osteosarcoma. The change can be passed on to children.
Acquired (somatic) changes. Most RB1 changes develop only in the tumor cells during a person’s life. These somatic changes are not inherited and cannot be passed on to children.

Which tumors have RB1 changes?

RB1 changes are found in several types of tumors. Common examples include:

Retinoblastoma. Almost all cases of retinoblastoma result from loss of both copies of RB1.
Small cell carcinoma. Nearly all small cell carcinomas of the lung have lost RB1. Loss of RB1 is also common in other fast-growing neuroendocrine carcinomas.
Osteosarcoma and other sarcomas. RB1 changes are found in many osteosarcomas and some other sarcomas.
Certain noncancerous fatty and fibrous tumors. A spindle cell lipoma, pleomorphic lipoma, and myofibroblastoma usually lose RB1. In these tumors, RB1 loss is a helpful diagnostic clue and does not mean cancer.
Other cancers. RB1 changes are found in some breast, bladder, and other cancers.

How do pathologists test for RB1?

Pathologists test for RB1 in two main ways:

Immunohistochemistry. Immunohistochemistry (IHC) uses an antibody to show whether cells are still making the Rb protein. Normal cells show brown nuclear staining. When tumor cells have lost RB1, their nuclei do not stain, while nearby normal cells still do.
Genetic testing. Molecular tests, such as next-generation sequencing, look directly at the RB1 gene for mutations or missing pieces. When an inherited change is suspected, testing is done on a blood or saliva sample.

What do RB1 results mean?

On an immunohistochemistry report, RB1 is usually described as “retained” or “lost”:

Retained (intact). The tumor cells are still making the Rb protein. This is the normal result for most tumors.
Lost (absent or deficient). The tumor cells are no longer making the Rb protein. This supports certain diagnoses, such as a spindle cell lipoma or small cell carcinoma. The meaning depends entirely on the tumor type.

In some breast cancers, loss of RB1 may affect how well certain targeted drugs work. Your oncologist can explain whether this applies to you. If a genetic test finds an inherited RB1 change, your doctor may recommend genetic counseling for you and your family.

Questions to ask your doctor

Why was RB1 tested on my sample?
Was RB1 retained or lost in my tumor?
What does the RB1 result mean for my diagnosis?
Is the RB1 change only in the tumor, or could it be inherited?
Should my family members or I have genetic counseling or testing?
Does the RB1 result affect my treatment options?
Do I need any further tests?