Stains & molecular markers
PAX8

Editorial Board Member: Gulisa Turashvili, M.D., Ph.D.
Editor-in-Chief: Debra L. Zynger, M.D.
Kelsey E. McHugh, M.D.

Topic Completed: 23 November 2020

Minor changes: 23 November 2020

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PubMed Search: PAX8 [title] stain pathology

Kelsey E. McHugh, M.D.
Page views in 2019: 46,627
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Cite this page: McHugh KE. PAX8. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/stainspax8.html. Accessed November 25th, 2020.
Definition / general
  • 1 of 9 members of paired box gene (PAX) family of transcription factors that regulate organogenesis (Am J Surg Pathol 2011;35:1473)
  • Involved in development of the central nervous system, eye, kidney, thyroid gland, organs derived from the mesonephric (Wolffian) duct and organs derived from the Müllerian duct (Mod Pathol 2011;24:751)
  • Structurally similar to PAX5 and PAX2 (Adv Anat Pathol 2012;19:140)
Essential features
  • Nuclear marker with expression in epithelial neoplasms of thyroid, thymic, ovarian, endometrial, endocervical, fallopian tube and renal origin
  • Variable expression in selected central nervous system tumors and sarcomas
  • Nuclear staining should be strong in intensity to be considered positive
  • Polyclonal and monoclonal antibodies against PAX8 exist
    • Polyclonal PAX8 antibodies are known to cross react with PAX5 (e.g. B cell lymphocytes, B cell lymphoma) and PAX6 (e.g. pancreatic islet cells, neuroendocrine tumors of select sites)
Terminology
  • Paired box gene 8
Pathophysiology
  • Gene is at 2p13 (NCBI: PAX8 [Accessed 26 October 2020])
  • PAX8 is comprised of an N terminal DNA binding domain, an octapeptide and a C terminal DNA binding domain (Biochem J 2004;377:553)
    • N terminal DNA binding domain is highly conserved among the PAX family of transcription factors
    • C terminal DNA binding domain is involved in transcriptional activation and repression activities
  • Polyclonal PAX8 antibodies are directed against the N terminus and, thus, are associated with cross reactivity with PAX2, PAX5 and PAX6 (Adv Anat Pathol 2012;19:140)
  • Monoclonal PAX8 antibodies are directed against the C terminus, which shares less homology amongst PAX proteins and, thus, is more specific for PAX8 (Appl Immunohistochem Mol Morphol 2013;21:59)
Clinical features
Interpretation
  • Nuclear stain
Uses by pathologists
  • Differentiate primary pulmonary carcinomas (PAX8-) from PAX8+ metastatic carcinomas (renal, Müllerian, thyroid) (Appl Immunohistochem Mol Morphol 2019 Feb;27:140)
  • Differentiate renal collecting duct carcinoma (PAX8+ / p63-) from urothelial carcinoma of the upper urinary tract (PAX8- / p63+) (Am J Surg Pathol 2010;34:965)
  • Differentiate anaplastic thyroid carcinoma (PAX8+) from other undifferentiated tumors of the head and neck (PAX8-) (Hum Pathol 2011;42:1873)
  • Differentiate hemangioblastoma (PAX8- / PAX2- / inhibin A+) from clear cell renal cell carcinoma (PAX8+ / PAX2+ / inhibin A-) metastatic to the CNS (Am J Surg Pathol 2011;35:262)
  • Differentiate endosalpingiosis / benign Müllerian inclusions (PAX8+) in lymph nodes from metastatic breast cancer (PAX8-) (Am J Surg Pathol 2010;34:1211)
  • Differentiate clear cell adenocarcinoma of the lower urinary tract (PAX8+) from urothelial carcinoma, urothelial carcinoma variants and adenocarcinoma of the urinary bladder or prostate (PAX8-) (Am J Surg Pathol 2008;32:1380)
  • Differentiate prostatic mesonephric remnant hyperplasia (PAX8+) from prostatic adenocarcinoma (PAX8-) (Am J Surg Pathol 2011;35:1054)
  • Differentiate primary thymic epithelial neoplasms (PAX8+) from other anterior mediastinal epithelial neoplasms (PAX8-) (Am J Surg Pathol 2011;35:1305)
  • Differentiate invasive micropapillary carcinoma of ovarian origin (PAX8+) from other common metastatic invasive micropapillary carcinomas, including those of the bladder, lung, breast, salivary gland and gastrointestinal tract (all PAX8-) (Am J Surg Pathol 2009;33:1037)
  • Differentiate ovarian carcinomas (PAX8+) from metastatic mammary carcinomas (PAX8-) (Am J Surg Pathol 2008;32:1566)
  • Differentiate Müllerian tumors (PAX8+) from other CK7 positive carcinomas, including breast and upper gastrointestinal tract (PAX8-) (Am J Clin Pathol 2011;136:428)
  • Differentiate pancreatic neuroendocrine tumor (PAX8+ / LEF1-) from pancreatic solid pseudopapillary neoplasm (PAX8- / LEF1+) (Appl Immunohistochem Mol Morphol 2020 Jan 31 [Epub ahead of print])
  • Differentiate ocular ciliary body epithelial and neuroepithelial tumors, including adenoma, adenocarcinoma and medulloepithelioma (PAX8+) from ocular melanocytic tumors (PAX8-) and retinal pigment epithelial neoplasms (PAX8-) (Ophthalmology 2020 Sep 28 [Epub ahead of print])
  • Differentiate thymic neuroendocrine carcinomas (PAX8+ / TTF1-) from pulmonary neuroendocrine carcinomas (PAX8- / TTF1+) (Mod Pathol 2013;26:1554)
  • Marker of nephrogenic adenoma (Am J Surg Pathol 2008;32:1380)
Microscopic (histologic) description
  • Strong, diffuse nuclear staining is the expected pattern of positivity
Microscopic (histologic) images

Contributed by Kelsey E. McHugh, M.D.
Metastatic renal cell carcinoma Metastatic renal cell carcinoma

Metastatic renal cell carcinoma

Metastatic ovarian serous carcinoma Metastatic ovarian serous carcinoma

Metastatic ovarian serous carcinoma

PAX8: endometrial CA, clear cell RCC

Endometrial adenocarcinoma, clear cell RCC



Contributed by Andrey Bychkov, M.D., Ph.D.

Ovarian cancer

Thyroid follicular cells

Papillary thyroid carcinoma

Virtual slides

Images hosted on other servers:

PAX8 in atypical polypoid adenomyoma

PAX8 in endometrial adenocarcinoma

Positive staining - normal
Positive staining - disease
Negative staining
Board review style question #1

A biopsy of 1 of multiple liver lesions in a 64 year old woman reveals metastatic carcinoma of unknown primary. The lesion is found to be strongly and diffusely CK7 and PAX8 positive. Carcinomas from which of the following primary sites of origin are PAX8 negative, thus eliminating this body site from the differential diagnosis?

  1. Endometrium
  2. Lung
  3. Ovary
  4. Thyroid
Board review answer #1
B. Lung

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Reference: PAX8
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