Stains & CD markers
PAX8
Copyright: 2002-2024, PathologyOutlines.com, Inc.
PubMed Search: PAX8 stain pathology
PAX8
Author: Kelsey E. McHugh, M.D.
Editorial Board Member: Gulisa Turashvili, M.D., Ph.D.
Editor-in-Chief: Debra L. Zynger, M.D.
Last author update: 23 November 2020
Last staff update: 1 September 2023
Copyright: 2002-2024, PathologyOutlines.com, Inc.
PubMed Search: PAX8 stain pathology
Table of Contents
Definition / general | Essential features | Terminology | Pathophysiology | Clinical features | Interpretation | Uses by pathologists | Microscopic (histologic) description | Microscopic (histologic) images | Positive staining - normal | Positive staining - disease | Negative staining | Board review style question #1 | Board review style answer #1Cite this page: McHugh KE. PAX8. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/stainsPAX8.html. Accessed April 23rd, 2024.
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)
- PAX5 is seen on B cells and in B cell lymphomas (Mod Pathol 2012;25:231)
- PAX6 is seen in pancreatic islet cells and pancreatic neuroendocrine tumors (Histochem Cell Biol 2011;136:595)
- 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
- PAX8 loss of function mutations cause congenital hypothyroidism (Eur J Endocrinol 2012;167:625, J Clin Endocrinol Metab 2001;86:234, J Clin Endocrinol Metab 2020 Oct 8 [Epub ahead of print])
- PAX8-PPARy gene rearrangements are seen in follicular variant thyroid carcinomas, noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP), follicular adenomas and papillary thyroid carcinomas (rare) (Semin Diagn Pathol 2020;37:213, J Clin Endocrinol Metab 2006;91:213, Am J Surg Pathol 2002;26:1016)
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. and Andrey Bychkov, M.D., Ph.D.
Metastatic renal cell carcinoma
Metastatic ovarian serous carcinoma
Endometrial adenocarcinoma, clear cell RCC
Ovarian cancer
Thyroid follicular cells
Papillary thyroid carcinoma
Positive staining - normal
- Renal tubular epithelium (Mod Pathol 2011;24:751, Appl Immunohistochem Mol Morphol 2011;19:293)
- Epithelium of the Müllerian tract, including epithelium of the ovary, fallopian tube, endometrium and endocervix (Mod Pathol 2011;24:751)
- Epithelium of the male genital tract, including rete testis, epididymis and seminal vesicle (Mod Pathol 2011;24:751)
- Thyroid follicular epithelium (Mod Pathol 2011;24:751)
- Renal pelvis and upper urethra (Mod Pathol 2011;24:751, Appl Immunohistochem Mol Morphol 2011;19:293)
- Ocular tissue, including normal corneal epithelium, iris sphincter pupillae muscle, iris pigment epithelium and dilator muscle complex (Ophthalmology 2020 Sep 28 [Epub ahead of print])
- Epithelium of thymus, though staining is weak (Am J Surg Pathol 2011;35:1305)
Positive staining - disease
- Clear cell renal cell carcinoma (Mod Pathol 2009;22:1218, Appl Immunohistochem Mol Morphol 2011;19:293)
- Papillary renal cell carcinoma (Mod Pathol 2009;22:1218, Appl Immunohistochem Mol Morphol 2011;19:293)
- Renal oncocytoma (81%) (Mod Pathol 2009;22:1218)
- Papillary thyroid carcinoma (Appl Immunohistochem Mol Morphol 2011;19:293)
- Follicular thyroid carcinoma (Appl Immunohistochem Mol Morphol 2011;19:293)
- Anaplastic thyroid carcinoma (Hum Pathol 2011;42:1873)
- Parathyroid adenoma (Appl Immunohistochem Mol Morphol 2011;19:293)
- Endometrial polyp, endometriosis, endosalpingiosis, paratubal cyst (Reprod Sci 2020;27:1580)
- Endometrial adenocarcinoma (Appl Immunohistochem Mol Morphol 2011;19:293)
- Expression is severely diminished in mucinous variants (44%)
- Endocervical adenocarcinoma (Appl Immunohistochem Mol Morphol 2011;19:293)
- Ovarian serous carcinoma (Appl Immunohistochem Mol Morphol 2011;19:293)
- Prostatic mesonephric remnant hyperplasia (Am J Surg Pathol 2011;35:1054)
- Nephrogenic adenoma, nephroblastoma (Am J Surg Pathol 2008;32:1380)
- Bladder clear cell adenocarcinoma (Am J Surg Pathol 2008;32:1380)
- Thymic epithelial neoplasms, including thymic carcinoma (77%), WHO type A thymomas (100%), and WHO type B thymomas (93%) (Am J Surg Pathol 2011;35:1305)
- Endolymphatic sac tumors (Head Neck Pathol 2019;13:355)
- Ocular ciliary body epithelial and neuroepithelial tumors (adenoma, adenocarcinoma, medulloepithelioma) (Ophthalmology 2020 Sep 28 [Epub ahead of print])
- Some sarcomas, including Ewing sarcoma (80%) (Sarcoma 2020;2020:3180798)
- A subset (56%) of nested variant urothelial carcinomas of the bladder has been described as having moderate to strong, patchy to diffuse nuclear positivity with PAX8 (Hum Pathol 2019;94:11)
- Rare (6%) high grade invasive ductal carcinomas of breast, mostly triple negative, may show weak to moderate nuclear staining (Appl Immunohistochem Mol Morphol 2021;29:293)
- Positivity has only been reported in subsets of mammary carcinoma interrogated with the monoclonal PAX8 antibody MRQ50 from Cell Marque (Appl Immunohistochem Mol Morphol 2021;29:293, Appl Immunohistochem Mol Morphol 2020;28:558, In Vivo 2022;36:473)
- Polyclonal PAX8 antibodies and the BC12 Biocare Medical monoclonal PAX8 antibody have not been reported to stain mammary carcinomas (Appl Immunohistochem Mol Morphol 2020;28:558, Am J Clin Pathol 2011;136:428, Am J Surg Pathol 2009;33:1037, Int J Gynecol Pathol 2015;34:257)
- Rare (7%) salivary duct carcinomas may demonstrate relatively diffuse moderate to strong nuclear staining (Appl Immunohistochem Mol Morphol 2021;29:680)
- Carcinoid tumors (due to cross reactivity): gastric / duodenal (100%), rectal (85%) (Am J Surg Pathol 2010;34:723)
- Neuroendocrine tumors (due to cross reactivity): duodenal (75%), pancreas (67%) (Mod Pathol 2011;24:412)
Negative staining
- Normal epithelium of bladder, lung, parathyroid, prostate, testis (Mod Pathol 2011;24:751)
- Carcinomas of the adrenal gland, bile ducts, breast, stomach, gastroesophageal junction, lung, pancreas, prostate, urothelial (Am J Surg Pathol 2011;35:816)
- Germ cell tumors (Mod Pathol 2011;24:751)
- Medullary thyroid carcinoma (Am J Surg Pathol 2011;35:816)
- Ocular melanocytic tumors and retinal pigment epithelial neoplasms (Ophthalmology 2020 Sep 28 [Epub ahead of print])
- B cells and B cell lymphomas (reported positive due to cross reactivity with PAX5 due to high sequence homology) (Mod Pathol 2012;25:231)
- Carcinoid tumor / neuroendocrine tumors of the ileum, lung and kidney (Hum Pathol 2011;42:1554, Mod Pathol 2011;24:412)
- Carcinoid tumor of the appendix (21%) and stomach (20%) are rarely positive due to cross reactivity (Am J Surg Pathol 2010;34:723)
- Neuroendocrine tumors of the rectum (29%), stomach (10%) and appendix (9%) are rarely positive due to cross reactivity (Mod Pathol 2011;24:412)
- Thymic neuroendocrine carcinomas (32% positive) (Mod Pathol 2013;26:1554)
- A minor subset of malignant mesothelioma (23%) is reported to have patchy to diffuse positivity in a cohort of cases in women (Am J Surg Pathol 2020 Aug 5 [Epub ahead of print])
- Most sarcomas, excluding rare cases of synovial sarcoma and solitary fibrous tumor (43% positive) (Sarcoma 2020;2020:3180798, Am J Surg Pathol 2011;35:1264, Appl Immunohistochem Mol Morphol 2019;27:e71, Appl Immunohistochem Mol Morphol 2019;27:195)
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?
- Endometrium
- Lung
- Ovary
- Thyroid
Board review style answer #1
