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A Comprehensive Analysis Of PAX8 Expression In Human Epithelial Tumors

Anna R. Laury, Ruth Perets, Huiying Piao, J. Krane, J. Barletta, C. French, L. Chirieac, Rosina L Lis, M. Loda, J. Hornick, R. Drapkin, M. Hirsch
Published 2011 · Biology, Medicine

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PAX8 is a paired-box gene important in embryogenesis of the thyroid, Müllerian, and renal/upper urinary tracts, and expression of PAX8 has been previously described in carcinomas from each of these sites. However, a large study including a wide variety of epithelial neoplasms from multiple organ sites other than the thyroid, kidney, or Müllerian system has not been performed. The goal of this study was to evaluate the utility of PAX8 immunostaining based on the evaluation of a wide range of epithelial tumors. PAX8 immunohistochemistry was performed on 1357 tumors (486 tumors in whole-tissue sections and 871 tumors in tissue microarrays, predominantly epithelial) from multiple organs. Only nuclear staining was scored as positive, and tumors were evaluated for the extent and intensity of staining. Western blot analysis with PAX8 was also performed on multiple tumor cell lines. Nuclear PAX8 staining was present in 91% (60 of 66) of thyroid tumors, 90% (158 of 176) of renal cell carcinomas (RCCs), 81% (13 of 16) of renal oncocytomas, 99% (164 of 165) of high-grade ovarian serous carcinomas, 71% (32 of 49) of nonserous ovarian epithelial neoplasms, 91% (10 of 11) of cervical epithelial lesions, and 98% (152 of 155) of endometrial adenocarcinomas. Of the remaining 719 evaluated tumors, only 30 cases (4%), including 12 thymic neoplasms, 3 bladder urothelial carcinomas, 4 lung squamous cell carcinomas, 2 esophageal adenocarcinomas, 1 pancreatic adenocarcinoma, 2 cholangiocarcinomas, 1 ovarian Sertoli-Leydig cell tumor, 1 ovarian sex cord stromal tumor, 3 testicular mixed germ cell tumors, and 1 acinic cell carcinoma, showed at least weak or focal PAX8 positivity. The unexpected finding was diffuse, moderate staining of PAX8 in a subset of thymomas and thymic carcinomas. The 689 remaining tumors, including but not limited to those from the prostate, colon, stomach, liver, adrenal gland, and head and neck, and small cell carcinomas from the lung, cervix, and ovary, were PAX8 negative. PAX8 specificity was confirmed by Western blot analysis, as expression was detected only in ovarian and RCC cell lines. These results show that PAX8 is a highly sensitive marker for thyroid, renal, Müllerian, and thymic tumors. Importantly, all lung adenocarcinomas, breast and adrenal neoplasms, and the majority of gastrointestinal tumors were negative for PAX8. Therefore, 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, RCC, and Wilms tumor-1, may be needed to distinguish between the 3 most common PAX8-positive tumors.
This paper references
10.1097/PGP.0b013e31817d5340
Distinguishing Breast Carcinoma From Müllerian Serous Carcinoma With Mammaglobin and Mesothelin
W. Kanner (2008)
10.1097/PAS.0b013e3181dc5e8a
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
R. Albadine (2010)
10.1038/modpathol.2009.88
Expression of PAX8 in normal and neoplastic renal tissues: an immunohistochemical study
G. Tong (2009)
10.1126/SCIENCE.289.5483.1357
PAX8-PPARgamma1 fusion oncogene in human thyroid carcinoma [corrected].
T. Kroll (2000)
10.1210/JC.2002-021907
RAS point mutations and PAX8-PPAR gamma rearrangement in thyroid tumors: evidence for distinct molecular pathways in thyroid follicular carcinoma.
M. Nikiforova (2003)
10.1097/PAS.0b013e3181da0a20
PAX8 Expression in Well-differentiated Pancreatic Endocrine Tumors: Correlation With Clinicopathologic Features and Comparison With Gastrointestinal and Pulmonary Carcinoid Tumors
K. B. Long (2010)
10.1002/dvdy.21867
FRS2α is required for the separation, migration, and survival of pharyngeal‐endoderm derived organs including thyroid, ultimobranchial body, parathyroid, and thymus
Y. Kameda (2009)
Pax8, a murine paired box gene expressed in the developing excretory system and thyroid gland.
D. Plachov (1990)
10.1016/S0168-9525(01)02594-X
Getting your Pax straight: Pax proteins in development and disease.
Neil C. Chi (2002)
10.1016/j.mce.2009.10.013
The role of the PAX8/PPARγ fusion oncogene in the pathogenesis of follicular thyroid cancer
N. L. Eberhardt (2010)
10.1097/PAS.0b013e3181962dcd
Immunohistochemical Panel to Identify the Primary Site of Invasive Micropapillary Carcinoma
T. Lotan (2009)
10.1016/j.ygyno.2009.08.023
Prognosis and hormone receptor status in older and younger patients with advanced-stage papillary serous ovarian carcinoma.
J. Liu (2009)
10.1038/modpathol.3800588
Immunohistochemical detection of WT1 protein in a variety of cancer cells
S. Nakatsuka (2006)
10.1200/JCO.2008.18.1107
New insights into the pathogenesis of serous ovarian cancer and its clinical impact.
K. Levanon (2008)
10.1097/PAS.0b013e31816d71ad
Expression of Pax8 as a Useful Marker in Distinguishing Ovarian Carcinomas From Mammary Carcinomas
D. Nonaka (2008)
10.1111/j.1600-0560.2010.01564.x
PAX8 discriminates ovarian metastases from adnexal tumors and other cutaneous metastases
M. Fujiwara (2010)
PAX8, a human paired box gene: isolation and expression in developing thyroid, kidney and Wilms' tumors.
A. Poleev (1992)
10.1038/NG0598-83
PAX8 mutations associated with congenital hypothyroidism caused by thyroid dysgenesis
P. E. Macchia (1998)
10.1097/PAS.0b013e3181e8ce5b
Xp11 Translocation Renal Cell Carcinoma (RCC): Extended Immunohistochemical Profile Emphasizing Novel RCC Markers
P. Argani (2010)
Am J Surg Pathol
Laury (2011)
PAX8-PP-ARgammal fusion oncogene in human thyroid carcinoma
T. Kroll (2000)
10.1111/j.1582-4934.2008.00594.x
Clinical significance of TTF‐1 protein expression and TTF‐1 gene amplification in lung adenocarcinoma
J. Barletta (2009)
10.1101/GAD.240102
Nephric lineage specification by Pax2 and Pax8.
M. Bouchard (2002)
10.1097/00000478-200407000-00014
OCT4 Staining in Testicular Tumors: A Sensitive and Specific Marker for Seminoma and Embryonal Carcinoma
T. Jones (2004)
10.1097/01.pgp.0000092130.10100.88
Wilms Tumor Gene Immunoreactivity in Primary Serous Carcinomas of the Fallopian Tube, Ovary, Endometrium, and Peritoneum
A. Hashi (2003)
10.1016/j.ydbio.2007.03.282
Pax2 and pax8 regulate branching morphogenesis and nephron differentiation in the developing kidney.
Melina Narlis (2007)
10.1002/dc.21426
Pax8: A marker for carcinoma of Müllerian origin in serous effusions
G. Tong (2011)
10.1210/JC.2004-1358
PAX8, TITF1, and FOXE1 gene expression patterns during human development: new insights into human thyroid development and thyroid dysgenesis-associated malformations.
Sylvia Sura Trueba (2005)
10.1210/EN.2006-1054
Congenital hypothyroid female pax8-deficient mice are infertile despite thyroid hormone replacement therapy.
J. Mittag (2007)
10.1210/JC.2002-021690
Involvement of the PAX8/peroxisome proliferator-activated receptor gamma rearrangement in follicular thyroid tumors.
T. Dwight (2003)
Mammaglobin, a mammary-specific member of the uteroglobin gene family, is overexpressed in human breast cancer.
M. Watson (1996)
10.1097/PAS.0b013e3181868904
Serous Tubal Intraepithelial Carcinoma and the Dominant Ovarian Mass: Clues to Serous Tumor Origin?
M. Roh (2009)
10.1016/S0955-0674(96)80087-1
Pax genes and their roles in cell differentiation and development.
A. Mansouri (1996)
10.1016/J.YGYNO.2006.08.052
Emerging roles for PAX8 in ovarian cancer and endosalpingeal development.
N. Bowen (2007)
10.1002/cncy.20089
Utility of paired box gene 8 (PAX8) expression in fluid and fine‐needle aspiration cytology
Ryan McKnight (2010)
10.1038/modpathol.2010.176
PAX8 expression reliably distinguishes pancreatic well-differentiated neuroendocrine tumors from ileal and pulmonary well-differentiated neuroendocrine tumors and pancreatic acinar cell carcinoma
A. Sangoi (2011)
10.1371/journal.pmed.0050232
Ovarian Carcinoma Subtypes Are Different Diseases: Implications for Biomarker Studies
M. Köbel (2008)
10.1038/onc.2009.402
Primary ex-vivo cultures of human fallopian tube epithelium as a model for serous ovarian carcinogenesis
K. Levanon (2010)
10.1097/00000478-200112000-00003
Diagnosing Primary and Metastatic Renal Cell Carcinoma: The Use of the Monoclonal Antibody `Renal Cell Carcinoma Marker'
D. K. McGregor (2001)
10.1097/PAS.0b013e31816b1020
Expression of PAX8 in Nephrogenic Adenoma and Clear Cell Adenocarcinoma of the Lower Urinary Tract: Evidence of Related Histogenesis?
G. Tong (2008)
10.1016/J.YPAT.2010.11.032
Are All Pelvic (Nonuterine) Serous Carcinomas of Tubal Origin
M. D. Post (2011)
10.1016/S0002-9440(10)63902-8
Genetic and biological subgroups of low-stage follicular thyroid cancer.
C. French (2003)
10.1155/2010/932371
Ovarian Cancer Pathogenesis: A Model in Evolution
A. Karst (2010)
10.1016/j.molonc.2009.01.004
Intercepting pelvic cancer in the distal fallopian tube: Theories and realities
C. Crum (2009)
10.1097/PAS.0b013e3181da7687
PAX8 Reliably Distinguishes Ovarian Serous Tumors From Malignant Mesothelioma
Anna R. Laury (2010)
The role of the PAX8/ PPARgamma fusion oncogene in the pathogenesis of follicular thyroid cancer
NL Eberhardt (2010)
10.1097/01.pai.0000213144.70148.8e
Expression of Renal Cell Carcinoma Antigen (RCC) in Renal Epithelial and Nonrenal Tumors: Diagnostic Implications
N. Bakshi (2007)
10.1038/modpathol.3801002
Diagnostic utility of thyroid transcription factors Pax8 and TTF-2 (FoxE1) in thyroid epithelial neoplasms
D. Nonaka (2008)
10.1593/NEO.91542
Overexpression of elafin in ovarian carcinoma is driven by genomic gains and activation of the nuclear factor kappaB pathway and is associated with poor overall survival.
A. Clauss (2010)



This paper is referenced by
Integrated Functional and Genomic Analysis of High-Grade Serous Ovarian Cancer
Mauricio Medrano (2015)
Immunohistochemical panel of glypican-3, hepatocyte paraffin antigen-1, arginase-1, cytokeratin-19, and human epithelial membrane antigen for the differential diagnosis of liver tumors
Kan Jiang (2019)
10.5772/intechopen.92554
Glucagonoma Masquerading as a Mucinous Cancer of the Ovary: Lessons from Cell Biology
Gwo Yaw Ho (2020)
10.1007/s13277-015-3964-3
The diagnostic utility of the triple markers Napsin A, TTF-1, and PAX8 in differentiating between primary and metastatic lung carcinomas
N. M. A. El-Maqsoud (2015)
10.1093/jnci/djy074
Perspectives on Ovarian Cancer From SEER: Today and Tomorrow.
D. Cramer (2019)
10.1007/978-1-4471-2942-4_5
Integration of Imaging and Pathology in the Multidisciplinary Process
J. A. Spencer (2014)
10.5826/dpc.0504a03
Metastatic papillary thyroid carcinoma to the nose: report and review of cutaneous metastases of papillary thyroid cancer
Philip R. Cohen (2015)
Metastatic carcinoMas to the Uterine cervix and corpUs
(2014)
10.1111/his.13757
SOX11: a potentially useful marker in surgical pathology: a systematic analysis of SOX11 expression in epithelial and non‐epithelial tumours
Sanpeng Xu (2019)
10.1097/PAS.0000000000000935
PAX8 Expression in a Subset of Malignant Peritoneal Mesotheliomas and Benign Mesothelium has Diagnostic Implications in the Differential Diagnosis of Ovarian Serous Carcinoma
D. Chapel (2017)
10.1007/s13691-016-0259-5
Late recurrence of gastric cancer in the ovary and uterine cervix
M. Watanabe (2016)
10.1097/PAP.0000000000000256
An Algorithmic Immunohistochemical Approach to Define Tumor Type and Assign Site of Origin
A. Bellizzi (2020)
10.1038/onc.2014.209
PAX genes in childhood oncogenesis: developmental biology gone awry?
P. Mahajan (2014)
THE ROLE AND MECHANISM OF THE HOMEOBOX GENE HOXA9 IN THE GROWTH OF EPITHELIAL OVARIAN CANCER
Song Yi Ko (2013)
10.1097/PCR.0000000000000149
Intraepithelial Neoplasia of the Fallopian Tube: Precursors, Field Effects, and Conceptual Traps
Emily E. K. Meserve (2016)
10.1016/j.path.2012.06.004
Metastases to and from the Breast.
A. Bombonati (2012)
10.1309/AJCP8WO2EOIAHSOF
The lung-restricted marker napsin A is highly expressed in clear cell carcinomas of the ovary.
P. L. Kandalaft (2014)
10.1507/endocrj.EJ18-0282
Utility of monoclonal PAX8 antibody for distinguishing intrathyroid thymic carcinoma from follicular cell-derived thyroid carcinoma.
A. Suzuki (2018)
The value of PAX8 and WT1 molecules in ovarian cancer diagnosis.
L. Liliac (2013)
10.1101/330597
Integrated Molecular Profiling Studies to Characterize the Cellular Origins of High-Grade Serous Ovarian Cancer
K. Lawrenson (2018)
Guidelines for Pathologic Diagnosis of Malignant Mesothelioma
Aliya N. Husain (2017)
10.1007/978-3-030-16518-5
Practical Breast Pathology: Frequently Asked Questions
Alexander D. Borowsky (2009)
10.1017/CBO9780511781049.030
Modern Soft Tissue Pathology: MERKEL CELL CARCINOMA AND METASTATIC AND SARCOMATOID CARCINOMAS INVOLVING SOFT TISSUE
Markku Miettinen (2010)
10.5795/JJSCC.55.355
PAX8 免疫染色が診断に有用であった Napsin A 陽性甲状腺癌による癌性胸膜炎の 1 例
正親 藤原 (2016)
10.1097/DAD.0b013e31823069cf
Cutaneous Metastases From Internal Malignancies: A Clinicopathologic and Immunohistochemical Review
I. Alcaraz (2012)
UNIVERSITY OF NAPOLI FEDERICO II
L. Nitsch (2015)
10.30928/2527-2039E-20202459
Carcinossarcoma de colo uterino - a dificuldade em se estabelecer o diagnóstico
César Cauê Bassetto (2020)
10.1016/j.humpath.2017.12.001
Vasitis nodosa and related lesions: a modern immunohistochemical staining profile with special emphasis on novel diagnostic dilemmas.
Brie Kezlarian (2018)
10.1017/CBO9781316167366.012
Metastatic carcinoma of unknown primary
P. Chu (2014)
10.1177/1933719119828095
PAX8: A Highly Sensitive Marker for the Glands in Extragenital Endometriosis.
Tomoko Arakawa (2019)
10.1016/J.MPDHP.2019.07.003
The expanding role of renal mass biopsy
S. Williamson (2019)
10.1097/PAI.0000000000000007
Value of GATA3 Immunostaining in the Diagnosis of Parathyroid Tumors
N. Ordóñez (2014)
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