Synonym: Paired box homeotic gene 2.
Nature: Nuclear transcriptional regulator in the paired-box family expressed during organogenesis of particularly the kidney and Müllerian tract.
Gene and structure: Chromosomal localization 10q24, MW 44.7 kDa, 416 amino acids, containing a DNA binding paired domain, a truncated homeodomain, an octapeptide region and a carboxyl-terminal transactivation domain.
Occurrence and function: PAX2 encodes a transcription factor crucial to the organogenesis and development of the urogenital tract, mammary glands, the central nervous system, eyes and ears. In these organs PAX2 regulates the expression of genes involved in mediating cell proliferation and growth, resistance to apoptosis, and cell migration. In the developing urogenital system PAX2 is widely expressed in the ductal and parenchymal components of the kidney and both wolffian- and müllerian-derived tissues. PAX2 is required for development and proliferation of renal tubules from blastema, and is expressed along with the mesenchyme-to-epithelium transition but in part disappears at the unset of terminal differentiation. In the adult kidney PAX2 is seen in glomerular parietal epithelial cells, distal convoluted tubules, Henle loops, and collecting ducts. PAX2 is upgraded in atrophic tubules. Proliferating bile ducts may be positive. PAX2 is constantly found in lymphocytes, mainly B-lymphocytes. In female, PAX2 is also found constantly in ovarian surface epithelium and inclusion cysts, fallopian tube epithelium, endometrial and endocervical glands, and mesonephric remnants. In male, PAX2 is also found in epididymis, vesicula seminalis and ejaculatory duct epithelial cells, while a weak and focal expression may be found in prostate.
+ Wilms’ tumour has been positive in few cases studied.
+/- When focal staining is included PAX2 is found in up to 85% of renal cell carcinomas (RCC) and oncocytoma, most prevalent in clear cell, papillary and collecting duct RCC. In some studies PAX2 has shown less prevalent in chromophobic carcinoma and oncocytoma and in metastatic RCC. Sarcomatoid parts of RCC are negative. Nephrogenic adenoma is mostly positive. Malignant lymphomas are generally positive irrespective of subtype.
–/+ PAX2 is less frequently found in uterine and ovarian endometrioid carcinoma (40%) and serous carcinoma (over-all 30-60%, low grade most frequently positive while high grade are positive in 10%), and in clear cell carcinoma. Metastatic tumours of Müllerian origin may express PAX2 in a larger proportion than primary tumours. Also parathyroid carcinoma and Wilms’ tumour is positive in many cases.
–(+)? Sporadic cases of PAX2 positive tumours are reported among hepatocellular carcinoma, colon adenocarcinoma, breast carcinoma, prostate adenocarcinoma, papillary cystadenoma of epididymis, endocervical carcinoma, malignant mesothelioma, testicular yolk sac tumour, and some soft tissue sarcomas.
Conflicting results have been published on breast carcinoma. Reports on a high proportion of positive cases probably are based on false positivity.
There are currently no good PAX2 ABs for IHC. As PAX8 appears to be currently the most sensitive and specific marker for renal cell carcinoma and ovarian non-mucinous carcinoma, a PAX8 Ab should be used.
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