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PAX8

Monday 5 July 2004

Definition: PAX8 is a paired-box gene important in embryogenesis of the thyroid, Müllerian tract, and renal/upper urinary tracts.

Pax8 is a transcription factor associated with the embryonic development of the thyroid gland, kidney, and the Müllerian system and plays a role in the tumorigenesis of these organs.

Pax8 has been shown to be expressed immunohistochemically in a high percentage of tumors of thyroid, renal, and Müllerian origin in both primary and metastatic sites.

Thyroid-specific transcription factors, Pax8, TTF-1, and TTF-2, are crucial for thyroid organogenesis and differentiation.

Expression in tumors

PAX8 is a paired-box gene important in embryogenesis of the thyroid, Müllerian tract, and renal/upper urinary tracts. Expression of PAX8 has been previously described in carcinomas from each of these sites.

PAX8 is a highly sensitive marker for thyroid tumors, renal tumors, Müllerian tumors, and thymic tumors. Importantly, all lung adenocarcinomas, breast and adrenal neoplasms, and the majority of gastrointestinal tumors are negative for PAX8.

PAX8 is an excellent marker for confirming primary tumor site. In a subset of cases, additional markers, including but not limited to thyroid transcription factor-1 (TTF1), RCC, and Wilms tumor-1 (WT1), may be needed to distinguish between the 3 most common PAX8-positive tumors.

- Pax8 is expressed in 79% of thyroid anaplastic carcinomas to a variable extent, whereas TTF-1 and TTF-2 were seen only in 18 and 7% of anaplastic carcinomas, respectively. (#18084247#)

- PAX8 expression in well-differentiated pancreatic endocrine tumors (PETs) (#20414099#)

  • PAXs (paired box) genes encode a family of transcription factors that regulate organogenesis and cell-lineage specification in multiple organ systems.
  • In the pancreas, PAXs proteins play a critical role in islet cell differentiation. We recently observed that islet cells show strong, diffuse staining for PAX8 by immunohistochemistry.
  • PAX8 is expressed in normal pancreatic islet cells and in a high proportion of primary and metastatic PETs.
  • In the GI tract, PAX8 is positive in the majority of duodenal and rectal carcinoid tumors, and in a minor subset of appendiceal and gastric carcinoids.
  • PAX8 expression is absent in ileal and pulmonary carcinoid tumors.
  • PAX8 immunostaining may be helpful in determining the primary site for a WDNET metastatic to the liver, as ileal (PAX8 negative) and pancreatic (PAX8 positive) tumors most often present as a metastasis from an occult primary.
  • PAX8 may also be a prognostic marker in PETs, as loss of expression is associated with malignant behavior.

- Positive immunoreactivity for Pax8 is noted in 77% of thymic carcinomas, 100% of WHO type A thymomas, and 93% of WHO type B thymomas. (#21836478#)

  • Consistent but weaker staining for Pax8 is also identified in the epithelial cells of remnant thymic tissue located in the periphery of the tumors. (#21836478#)

Immunochemistry

- PAX8 (+)/p63 (-) immunostaining pattern in renal collecting duct carcinoma (CDC) is a useful immunoprofile in the differential diagnosis of CDC versus urothelial carcinoma of upper urinary tract. (#20463571#)

Pathology

- PAX8/PPARG fusion gene in thyroid follicular tumors

See also

- PAXs

References

- Pax8 expression in thymic epithelial neoplasms: an immunohistochemical analysis. Weissferdt A, Moran CA. Am J Surg Pathol. 2011 Sep;35(9):1305-10. PMID: #21836478#

- A Comprehensive Analysis of PAX8 Expression in Human Epithelial Tumors. Laury AR, Perets R, Piao H, Krane JF, Barletta JA, French C, Chirieac LR, Lis R, Loda M, Hornick JL, Drapkin R, Hirsch MS. Am J Surg Pathol. 2011 May 5. PMID: #21552115#

- 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. Albadine R, Schultz L, Illei P, Ertoy D, Hicks J, Sharma R, Epstein JI, Netto GJ. Am J Surg Pathol. 2010 Jul;34(7):965-9. PMID: #20463571#

- PAX8 Expression in well-differentiated pancreatic endocrine tumors: correlation with clinicopathologic features and comparison with gastrointestinal and pulmonary carcinoid tumors. Long KB, Srivastava A, Hirsch MS, Hornick JL. Am J Surg Pathol. 2010 May;34(5):723-9. PMID: #20414099#

- Diagnostic utility of thyroid transcription factors Pax8 and TTF-2 (FoxE1) in thyroid epithelial neoplasms. Nonaka D, Tang Y, Chiriboga L, Rivera M, Ghossein R. Mod Pathol. 2008 Feb;21(2):192-200. PMID: #18084247#