(Paired box gene-2 protein)

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.

Selected references

Albadine R, Schultz L, Illei P, Ertoy D, Hicks J, Sharma R, Epstein JI, Netto GJ. PAX8 (+)/p63 (-) immunostaining pattern in renal collecting duct carcinoma (CDC): a useful immunoprofile in the differential diagnosis of CDC versus urothelial carcinoma of upper urinary tract. Am J Surg Pathol. 2010 Jul;34(7):965-9. PubMed PMID: 20463571. Bowen NJ, Logani S, Dickerson EB, Kapa LB, Akhtar M, Benigno BB, McDonald JF. Emerging roles for PAX8 in ovarian cancer and endosalpingeal development. Gynecol Oncol. 2007 Feb;104(2):331-7. Epub 2006 Oct 24. PubMed PMID: 17064757. Fujiwara M, Taube J, Sharma M, McCalmont TH, Kim J. PAX8 discriminates ovarian metastases from adnexal tumors and other cutaneous metastases. J Cutan Pathol. 2010 Sep;37(9):938-43. Epub 2010 May 19. PubMed PMID: 20492080. Laury AR, Hornick JL, Perets R, Krane JF, Corson J, Drapkin R, Hirsch MS. PAX8 reliably distinguishes ovarian serous tumors from malignant mesothelioma. Am J Surg Pathol. 2010 May;34(5):627-35. PubMed PMID: 20414098. Long KB, Srivastava A, Hirsch MS, Hornick JL. PAX8 Expression in well-differentiated pancreatic endocrine tumors: correlation with clinicopathologic features and comparison with gastrointestinal and pulmonary carcinoid tumors. Am J Surg Pathol. 2010 May;34(5):723-9. PubMed PMID: 20414099. Nonaka D, Chiriboga L, Soslow RA. Expression of pax8 as a useful marker in distinguishing ovarian carcinomas from mammary carcinomas. Am J Surg Pathol. 2008 Oct;32(10):1566-71. PubMed PMID: 18724243. Pellizzari L, Puppin C, Mariuzzi L, Saro F, Pandolfi M, Di Lauro R, Beltrami CA, Damante G. PAX8 expression in human bladder cancer. Oncol Rep. 2006 Nov;16(5):1015-20. PubMed PMID: 17016586. Sangoi AR, Karamchandani J, Kim J, Pai RK, McKenney JK. The use of immunohistochemistry in the diagnosis of metastatic clear cell renal cell carcinoma: a review of PAX-8, PAX-2, hKIM-1, RCCma, and CD10. Adv Anat Pathol. 2010 Nov;17(6):377-93. PubMed PMID: 20966644. Tabrizi AD, Kalloger SE, Köbel M, Cipollone J, Roskelley CD, Mehl E, Gilks CB. Primary ovarian mucinous carcinoma of intestinal type: significance of pattern of invasion and immunohistochemical expression profile in a series of 31 cases. Int J Gynecol Pathol. 2010 Mar;29(2):99-107. PubMed PMID: 20173494. Tong GX, Devaraj K, Hamele-Bena D, Yu WM, Turk A, Chen X, Wright JD, Greenebaum E. PAX8: A marker for carcinoma of Müllerian origin in serous effusions. Diagn Cytopathol. 2010 Jul 6. [Epub ahead of print] PubMed PMID: 20607683. Tong GX, Yu WM, Beaubier NT, Weeden EM, Hamele-Bena D, Mansukhani MM, O'Toole KM. Expression of PAX8 in normal and neoplastic renal tissues: an immunohistochemical study. Mod Pathol. 2009 Sep;22(9):1218-27. Epub 2009 Jun 12. PubMed PMID: 19525927. Wiseman W, Michael CW, Roh MH. Diagnostic utility of PAX8 and PAX2 immunohistochemistry in the identification of metastatic Müllerian carcinoma in effusions. Diagn Cytopatol. 2010 Oct 14. [Epub ahead of print] PubMed PMID: 20949455. Zhang P, Zuo H, Nakamura Y, Nakamura M, Wakasa T, Kakudo K. Immunohistochemical analysis of thyroid-specific transcription factors in thyroid tumors. Pathol Int. 2006 May;56(5):240-5. PubMed PMID: 16669872.

13.03.12 - MV/LE