PAX8

PAX8 is a protein that helps control the activity of genes in certain types of cells. It acts as a transcription factor, meaning it turns genes on or off to guide how cells grow, develop, and function. PAX8 is especially important during early development and is involved in forming organs such as the thyroid gland, kidneys, female reproductive organs, and parts of the nervous system. Because of its key role in these tissues, PAX8 is often used by pathologists as a marker to help determine where a tumour started.

What types of normal cells and tissues express PAX8?

PAX8 is normally found in the nucleus of cells in the following tissues:

• Thyroid gland (specifically, follicular cells).

• Kidneys (tubular epithelium).

• Female reproductive organs, including the ovary, fallopian tube, endometrium, and endocervix.

• Male reproductive system, including the epididymis and seminal vesicles.

• Thymus (in some types of epithelial cells).

• Ocular (eye) tissue, including the ciliary body.

In these tissues, PAX8 plays a role in regulating cell growth and function. It is not typically found in the lungs, gastrointestinal tract, bladder, prostate, or breast.

How do pathologists test for PAX8?

Pathologists test for PAX8 using a technique called immunohistochemistry (IHC). In this test, antibodies are applied to a tissue sample. If PAX8 is present, the antibodies attach to it, producing a visible colour change that can be seen under the microscope. PAX8 shows up as a nuclear stain (a colour change in the cell’s nucleus). A strong, clear nuclear stain indicates that the cells are positive for PAX8. If there is no staining, the result is negative.

There are different types of antibodies used to test for PAX8. Some are called polyclonal antibodies, which may also react with related proteins like PAX5 and PAX6, potentially causing confusion in certain cases. Other tests use monoclonal antibodies, which are more specific to PAX8 and reduce the chance of cross-reactions.

What types of tumours express PAX8?

PAX8 is commonly found in tumours that develop from the thyroid, kidney, and female reproductive tract. These include:

• Thyroid cancers: papillary, follicular, and anaplastic thyroid carcinoma.

• Kidney cancers: clear cell, papillary, and chromophobe renal cell carcinoma; renal oncocytoma.

• Endometrial and endocervical adenocarcinoma.

• Ovarian carcinomas, including high-grade serous carcinoma.

• Clear cell adenocarcinoma of the urinary tract.

• Thymic epithelial tumours, such as thymoma and thymic carcinoma.

• Nephrogenic adenoma and nephroblastoma.

PAX8 can also be seen in some neuroendocrine tumours of the pancreas and gastrointestinal tract (though often due to cross-reaction) and in a subset of sarcomas such as Ewing sarcoma.

It is not usually expressed in cancers of the lung, bladder, breast, prostate, or gastrointestinal tract (unless due to cross-reaction), making it helpful for distinguishing between tumours that may look similar under the microscope.

Why is PAX8 important in a pathology report?

PAX8 is a valuable tool for helping pathologists determine the origin of a tumour, especially when it has spread from another part of the body (metastasis). For example:

• In a lung mass, if the tumour is PAX8 positive, it may actually have come from the kidney, ovary, or thyroid—not the lung itself.

• In the urinary tract, PAX8 helps distinguish renal cell carcinoma (PAX8 positive) from urothelial carcinoma (PAX8 negative).

• In female pelvic cancers, PAX8 can help confirm that the tumour started in the uterus, ovary, or fallopian tube.

This information is critical for making an accurate diagnosis and choosing the most effective treatment. In some cases, the pattern of PAX8 staining may also provide insight into how the tumour might behave or respond to therapy.

Questions to ask your doctor

• What does the PAX8 result mean in my pathology report?

• Does the presence of PAX8 suggest where my cancer started?

• Could PAX8 staining affect my diagnosis or treatment plan?

• Are any additional tests needed to confirm where the tumour came from?