Definition: PAX8 is a paired-box gene important in embryogenesis of the thyroid, Müllerian tract, and renal/upper urinary tracts.
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.
Pathology
PAX8/PPARG fusion gene in thyroid follicular tumors
See also
References
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 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