PAX8

The Pathology Dictionary Team
May 22, 2023

What is PAX8?

PAX8  (Paired box gene 8) is a specialized protein called a transcription factor. It plays an important role in the formation of various organs including the thyroid gland, kidneys, ovaries, fallopian tubes, uterus, and vagina.

What does PAX8 do?

The PAX8 protein is required for the normal development and function of various organs including the thyroid gland, kidneys, ovaries, fallopian tubes, uterus, and vagina. In the thyroid gland, PAX8 regulates the expression of genes that are necessary for the production of thyroid hormones, such as thyroxine (T4) and triiodothyronine (T3).

What types of normal cells express PAX8?

PAX8 is expressed by normal, healthy cells in the thyroid gland, kidneys, ovaries, fallopian tubes, uterus, and vagina. PAX8 is also expressed by some types of immune cells.

Organs that normally show expression of PAX8 include:

• Thyroid gland: PAX8 is crucial for the development, differentiation, and function of thyroid cells. It regulates the expression of genes involved in thyroid development, such as TTF-1 (Thyroid Transcription Factor-1) and TTF-2. PAX8 is required for the formation of the thyroid follicular cells and the production of thyroid hormones (T4 and T3).
• Kidney: PAX8 is involved in kidney development and maintenance. It plays a role in the formation of the renal tubules and regulates the expression of genes that are essential for kidney function, including genes involved in renal epithelial cell differentiation and transport processes.
• Müllerian tract: The Müllerian tract refers to the embryonic precursor structures that give rise to female reproductive organs, such as the ovaries, fallopian tubes, uterus, and upper part of the vagina. PAX8 is expressed in these tissues and is necessary for their normal development.

What types of tumours express PAX8?

PAX8 expression is commonly seen in a wide variety of noncancerous and cancerous tumours, and its immunohistochemical detection is often used as a diagnostic marker for these types of tumours.

Tumours that express PAX8 include:

• Thyroid gland tumours: PAX8 is expressed in most noncancerous and cancerous types of thyroid gland tumours including papillary thyroid carcinoma, follicular thyroid carcinoma, poorly differentiated thyroid carcinoma, follicular thyroid adenoma, oncocytic thyroid carcinoma, and oncocytic thyroid adenoma.
• Kidney tumours: PAX8 is expressed by many types of noncancerous and cancerous kidney tumours including clear cell renal cell carcinoma.
• Mullerian tract tumours: PAX8 is expressed in various types of noncancerous and cancerous tumours that arise in the Müllerian tract, an area of the body that includes the ovaries, fallopian tubes, uterus, and vagina.

It’s important to note that while PAX8 expression is observed in these tumour types, it should be interpreted in conjunction with other clinical and pathological features for accurate diagnosis and management.

What tests do pathologists perform to look for PAX8?

Pathologists use a test called immunohistochemistry to ‘see’ PAX8 protein inside cells. The PAX8 protein is normally found in a part of the cell called the nucleus. 

What does positive for PAX8 mean?

Positive for PAX8 means that the PAX8 protein was seen inside the cells of interest in the tissue sample. Reactive is another term that pathologists use to describe cells that are producing PAX8. 

What does negative for PAX8 mean?

Negative for PAX8 means that the PAX8 protein was not seen inside the cells of interest in the tissue sample. Non-reactive is another term that pathologists use to describe cells that are not producing PAX8.