Nature: Nuclear transcriptional regulator in the paired-box family expressed during organogenesis of the thyroid gland, kidney, and Müllerian tract.
Gene and structure: Chromosomal localization 2q13, Molecular weight of the unprocessed precursor 48 kDa, of five isoforms 31-42 kDa.
Occurrence and function: PAX8 is a transcription factor crucial to the organogenesis and development of the thyroid gland, urogenital tract, placenta and inner ear. In the thyroid, PAX8 is a master gene that regulates maintenance of the differentiated thyroid follicular cell phenotype, where it controls and activates the transcription of the main proteins responsible for the functional activity of follicular cells such as thyroglobulin, thyroperoxidase and sodium/iodide symporter. In the developing kidney PAX8 is important for renal vescicle formation. PAX8 regulates the expression of the WT1 gene.
Follicular and papillary thyroid carcinoma are virually always PAX8 positive (while anaplastic carcinoma is positive in most cases and medullary thyroid carcinoma negative). PAX8 is also found in almost all cases of ovarian serous, endometrioid, transitional and clear cell carcinoma (while mucinous carcinoma is positive in a minor number of cases), and endometrial carcinoma.
PAX8 is found in most cases of all types of renal cell carcinoma and in oncocytoma as well as in thymic tumours.
PAX8 is found in a varying proportion of pancreatic, duodenal and rectal neuroendocrine tumour, while gastric NET are less often positive (and pulmonary and ileal NETs virtually never positive). PAX8 is also found in a minor number of lung squamous cell carcinoma.
Sporadic cases of gastrointestinal adenocarcinomas, uterine cervical neoplasia, seminoma and malignant mesothelioma are reported positive. There are conflicting data on the positivity in urothelial carcinoma.
Adenocarcinomas of lung and breast have consistently been reported negative.
PAX8 appears to be currently the most sensitive and specific marker for renal cell carcinoma and ovarian non-mucinous carcinoma.
Fallopian tube and kidney are both recommended as positive tissue controls for PAX8. In fallopian tube the
protocol must be calibrated to provide an at least weak to moderate, distinct nuclear staining of the
majority of the ciliated epithelial cells and a strong nuclear staining of the intercalated secretory epithelial cells. A weak cytoplasmic staining in the intercalated secretory epithelial cells can be expected and must be accepted. In kidney, optimally calibrated protocols must show an at least weak to moderate, distinct nuclear staining in the epithelial cells of the proximal and distal renal tubules, loops of Henle, collecting ducts, and the parietal epithelial cells of Bowman’s capsule. A weak cytoplasmic staining in the same cells can be expected.
Laury AR. et al. A comprehensive analysis of PAX8 expression in human epithelial tumors. - Am. J. Surg. Pathol. 2011;6:816-26 Link
Tacha D. et al. Expression of PAX8 in normal and neoplastic tissues: a comprehensive immunohistochemical study. - Appl. Immunohistochem. Mol. Morphol. 2011;4:293-9 Link