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PAX8
Monday 5 July 2004
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Definition: PAX8 is a paired-box gene important in embryogenesis of the thyroid, Müllerian tract, and renal/upper urinary tracts.
Images
FNA of extraovarian primary peritoneal carcinoma metastatic to supraclavicular lymphnode ER+ PAX8+
Function
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. Thyroid-specific transcription factors, Pax8, TTF-1, and TTF-2, are crucial for thyroid organogenesis and differentiation.
Expression
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.
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 expression in thyroid tumors
- thyroid SCC / thyroid squamous cell carcinoma
PAX8 expression in parathyroid tumors : PAX8-expressing tumors
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.
PAX-8 is key if differential is lung adenocarcinoma vs. thyroid carcinoma.
- 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.
thymic tumors
- 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)
extraovarian primary peritoneal carcinoma (EOPPC)
- example : FNA of extraovarian primary peritoneal carcinoma metastatic to supraclavicular lymphnode ER+ PAX8+ : https://twitter.com/pathologyfinder/status/768395560562876416
- ovarian serous carcinoma (96.4%)
- ovarian endometrioid carcinoma (88.9%)
- ovarian clear cell carcinoma (100%)
- ovarian mucinous carcinoma (8.3%)
endometrial tumors
endocervical tumors
Merkel cell carcinoma
nephrogenic adenoma
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)
A GRIA2 and PAX8-positive renal solitary fibrous tumor with NAB2-STAT6 gene fusion. (26337721)
PAX-8 immunostain on a lung nodule : Same staining intensity as the thyroid primary tumor .
Negative PAX8 in a lung tumor
- A lung carcinoma is never strongly and diffusely positive for PAX-8.
- PAX8 differentiates PAX8+ primary or metastatic tumors (kidney, Mullerian [but not mucinous, Am J Surg Pathol 2011;35:1837], thymic, thyroid) from PAX8- tumors (adrenal, breast, GI [most], lung, prostate, Am J Surg Pathol 2011;35:816)
Differentiate prostatic mesonephric remnant hyperplasia (PAX8+) from prostatic adenocarcinoma (PAX8-, Am J Surg Pathol 2011;35:1054)
- PAX8 differentiates metastatic clear cell renal cell carcinoma (PAX2+ or PAX8+ / inhibinA neg) from hemangioblastoma (PAX2-, PAX8-, inhibin A+, Am J Surg Pathol 2011;35:262)
- PAX8 differentiates endosalpingiosis in axillary lymph nodes (PAX8+ / WT1+) from metastatic breast carcinoma (PAX8-, WT1-, Am J Surg Pathol 2010;34:1211)
- PAX8 differentiates renal collecting duct carcinoma (PAX8+ / p63-) from urothelial carcinoma of upper urinary tract (PAX8- / p63+, Am J Surg Pathol 2010;34:965)
- PAX8 differentiates thyroid anaplastic carcinoma (PAX8+) from head and neck squamous cell carcinoma (PAX8-, Hum Pathol 2011;42:1873)
PAX8 determines primary site of invasive micropapillary carcinomas as part of panel (Am J Surg Pathol 2009;33:1037)
PAX8 is a Marker of nephrogenic adenoma
PAX8 determines renal tubular origin of various disease processes (Am J Surg Pathol 2011;35:1264)
Pathology
PAX8-PPARG fusion gene
- PAX8-PPARG fusion gene in thyroid follicular tumors
- PAX8 and PPARG fusion gene is found in follicular lesions: follicular carcinoma, some follicular adenomas and follicular variants of papillary carcinoma.
Open references
A GRIA2 and PAX8-positive renal solitary fibrous tumor with NAB2-STAT6 gene fusion. Ichiyanagi O, Ito H, Takai S, Naito S, Kato T, Nagaoka A, Yamakawa M. Diagn Pathol. 2015 Sep 4;10(1):155. doi : 10.1186/s13000-015-0386-x PMID: 26337721 (Free)
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
