PAX5

PAX5 is a protein that acts as a transcription factor, which means it helps control when certain genes are turned on or off in a cell. It plays an important role in the early development of the immune system by guiding immature blood cells to become B cells, a type of white blood cell that helps the body fight infections. Because of its close link to B cell development, PAX5 is also known as the B-cell lineage-specific activator protein (BSAP).

What does PAX5 do?

PAX5 is essential for the formation and function of B cells. It turns on genes that are necessary for B cell development and turns off genes that belong to other types of blood cells. It is also involved in other important biological processes, including the development of the brain and male reproductive cells (sperm). In diseases like cancer, abnormal activity or loss of PAX5 can interfere with the normal development of B cells and contribute to the growth of blood cancers.

Where is PAX5 normally found or active?

PAX5 is normally found in the nucleus of immature and mature B cells. It is present in nearly all B cells except plasma cells, which are the final stage of B cell development and no longer need PAX5. PAX5 is also active during early brain development and in certain cells of the testis. In healthy tissues, pathologists see PAX5 staining mainly in the nucleus of B cells.

Why is PAX5 important in disease?

PAX5 is important because it helps pathologists identify cancers that come from B cells. These cancers are called B cell lymphomas or B cell leukemias. PAX5 is usually present in both early-stage and mature B cell cancers. In some cases, it may be the only marker of B cell origin—especially when other markers like CD20 are missing (such as after treatment with certain medications or in specific diseases like Hodgkin lymphoma or B lymphoblastic leukemia).

In addition to B cell cancers, PAX5 can sometimes be seen in other types of tumours, such as Merkel cell carcinoma, small cell lung cancer, and acute myeloid leukemia with specific genetic changes. However, these are exceptions, and pathologists interpret PAX5 results carefully depending on the clinical situation.

How do pathologists test for PAX5?

Pathologists test for PAX5 using a technique called immunohistochemistry (IHC). This method uses antibodies that stick to the PAX5 protein in a tissue sample. If PAX5 is present, it shows up as a nuclear stain (colour change in the nucleus) when the sample is viewed under a microscope. A positive result means PAX5 is present and usually confirms that the cells are of B cell origin. A negative result means the cells do not express PAX5, which may suggest they are not B cells or are at a later stage (like plasma cells).

PAX5 testing is especially useful when the diagnosis is unclear, or when B cell markers such as CD20 are absent due to treatment or unusual tumour behaviour.

What types of tumours express PAX5?

PAX5 is strongly expressed in most B cell lymphomas and leukemias, including:

• Diffuse large B cell lymphoma

• Follicular lymphoma

• Burkitt lymphoma

• Chronic lymphocytic leukemia / small lymphocytic lymphoma

• Mantle cell lymphoma

• Marginal zone lymphomas

• Primary mediastinal large B cell lymphoma

• Hairy cell leukemia

• B lymphoblastic leukemia / lymphoma

• Classic Hodgkin lymphoma

• Nodular lymphocyte predominant Hodgkin lymphoma

It may also be expressed in:

• Merkel cell carcinoma (a type of skin cancer)

• Small cell lung carcinoma

• Acute myeloid leukemia with a specific genetic change called t(8;21)

• Rectal neuroendocrine tumours (in the cytoplasm, not nucleus)

PAX5 is usually negative in plasma cell tumours, T cell and NK cell lymphomas, and most non-blood-related (nonhematologic) cancers.

Why is PAX5 important in a pathology report?

PAX5 is important because it helps determine whether a cancer is made up of B cells. This information is critical for diagnosing the correct type of lymphoma or leukemia, especially when other markers are missing or unclear. Identifying B cell origin helps guide treatment decisions, which may include chemotherapy, targeted therapy, or immunotherapy.

PAX5 can also help distinguish between different types of cancer when a tumour looks similar under the microscope. For example, it can help differentiate B cell lymphomas from T cell lymphomas or myeloid cancers. In some rare tumours, PAX5 expression may provide clues about aggressive behaviour or prognosis.

Questions to ask your doctor

• What does the PAX5 result in my pathology report mean?

• Does the PAX5 result confirm that my tumour is a B cell lymphoma or leukemia?

• How does this result affect my diagnosis and treatment options?

• Were other B cell markers tested along with PAX5?

• Is further testing needed to better understand the type of cancer I have?