Paired box gene-8 protein (PAX8)

Characteristics

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.
 

Neoplasms

+
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.
 

Application

PAX8 appears to be currently the most sensitive and specific marker for renal cell carcinoma and ovarian non-mucinous carcinoma.

Visualization

Abs: Currently recommendable Abs are mAb clones MRQ-50, BC12 and pAbs (Biocare, Cell Marque and Protein Techgroup). BC12 is directed against the C-terminal  part of PAX8, the others probaly against the N-terminal part, giving cross reaction with a PAX5 epitope.
Antigen retrieval: HIER is mandatory, an alkaline buffer is preferable.
Control: Normal kidney: most nuclei in distal tubules/collecting ducts must show a distinct staining reaction. A weak cytoplasmic reaction may occur.
 

Assessments

Run 34 2012

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.