PAX-8

What is PAX-8?

PAX-8 (stands for ‘paired box gene 8’) is a specialized protein that is produced by normal cells in the thyroid gland, thymus, ovary, fallopian tube, uterus, bladder, and kidneys. The ovaries, fallopian tubes, and uterus are sometimes grouped together under the terms ‘female genital tract’ or ‘Müllerian tract’. Tumors that start from one of these organs may also produce PAX-8.

What tests do pathologists perform to look for PAX-8?

Pathologists use a test called immunohistochemistry to ‘see’ PAX-8 protein inside cells. The PAX-8 protein is normally found in a part of the cell called the nucleus. 

What does positive for PAX-8 mean?

Positive for PAX-8 means that the PAX-8 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 PAX-8. 

What does negative for PAX-8 mean?

Negative for PAX-8 means that the PAX-8 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 PAX-8. 

Why do pathologists test for PAX-8?

Pathologists often perform immunohistochemistry for PAX-8 to determine if the cells that they are seeing under the microscope come from one of the organs or tissues that normally produce this protein. This is particularly important when examining tumour cells that have spread to another part of the body (this type of spread is called metastasis). If the tumour cells are positive for PAX-8, it suggests that the tumour may have started in the thyroid gland, thymus, ovary, fallopian tube, uterus, bladder, or kidneys. In contrast, if the cells are negative for PAX-8, it suggests that the tumour may have come from an organ or type of tissue that does not normally produce PAX-8.

Normal types of tissues and cells that produce PAX-8

• Kidney: tubular cells
• Müllerian tract: epithelium of the ovary, fallopian tube, endometrium, and cervix
• Thyroid: follicular cells

Tumours that frequently produce PAX-8

• Kidney cancers including clear cell renal cell carcinoma, papillary renal cell carcinoma, and Wilms’s tumor
• Thyroid cancers including papillary thyroid carcinoma, follicular carcinoma, and anaplastic thyroid carcinoma
• Uterine cancers including endometrioid carcinoma, serous carcinoma, and clear cell carcinoma
• Ovarian cancers including high-grade serous carcinoma, low-grade serous carcinoma, clear cell carcinoma, endometrioid carcinoma
• Endocervical adenocarcinoma