Abstract
PAX8 is a transcription factor involved in the regulation of organogenesis of the thyroid gland, kidney, and Müllerian system. It is commonly expressed in epithelial tumors of thyroid and parathyroid glands, kidney, thymus, and female genital tract. PAX8 is increasingly used in the establishment of tissue of origin in carcinomas and has recently been identified in a subset of small blue round cell tumors including Ewing sarcomas/PNETs. However, it is unclear if this association in ES/PNETs is due to renal origin or is PNET specific. In this study we investigated the PAX8 staining pattern of primary renal and extra-renal ES/PNETs to explore its potential diagnostic and prognostic role. A tissue microarray (TMA) of 22 cases of extra-renal Ewing/PNETs and two separate cases of primary renal PNET whole slide sections were immunohistochemically stained with rabbit polyclonal PAX8 antibody. PAX8 was positive in 2 of 2 primary renal PNETs and in 14 (64 %) cases of the extra renal PNETs. The association between PAX8 immunoreactivity and Ewing/PNET was identified in both primary renal and extra-renal Ewing/PNETs for the first time. Further studies are warranted to verify these findings and to shed light in the tumorigenesis of Ewing/PNET. However, PAX8 is not useful in establishing a diagnosis of Ewing/PNET due to its presence in different tumors like carcinomas, lymphomas and sarcomas. PAX8 does not seem to have prognostic value.
Similar content being viewed by others
References
Plachov D, Chowdhury K, Walther C, Simon D, Guenet JL, Gruss P (1990) PAX8, a murine paired box gene expressed in the developing excretory system and thyroid gland. Development 110(2):643–651
Tacha D, Zhou D, Cheng L (2011) Expression of PAX8 in normal and neoplastic tissues: a comprehensive immunohistochemical study. Appl Immunohistochem Mol Morphol 19(4):293–299
Laury AR, Perets R, Piao H, Krane JF, Barletta JA, French C, Chirieac LR, Lis R, Loda M, Hornick JL, Drapkin R, Hirsch MS (2011) A comprehensive analysis of PAX8 expression in human epithelial tumors. Am J Surg Pathol 35(6):816–826
Koo J, Mertens RB, Mirocha JM, Wang HL, Dhall D (2012) Value of islet 1 and PAX8 in identifying metastatic neuroendocrine tumors of pancreatic origin. Mod Pathol 25(6):893–901
Ordóñez NG (2012) Value of PAX8 immunostaining in tumor diagnosis: a review and update. Adv Anat Pathol 19(3):140–151
Tan PH, Cheng L, Rioux-Leclercq N, Merino MJ, Netto G, Reuter VE, Shen SS, Grignon DJ, Montironi R, Eqevad L, Srigley JR, Delahunt B, Moch H, ISUP Renal Tumor Panel (2013) ISUP renal tumor panel. Renal tumors: diagnostic and prognostic biomarkers. Am J Surg Pathol 37(10):1518–1531
Chang A, Brimo F, Montgomery EA, Epstein JI (2013) Use of PAX8 and GATA3 in diagnosing sarcomatoid renal cell carcinoma and sarcomatoid urothelial carcinoma. Hum Pathol 44(8):1563–1568
Carney EM, Banerjee P, Ellis CL, Albadine R, Sharma R, Chaux AM, Burger PC, Netto GJ (2011) PAX2(−)/PAX8(−)/inhibin A(+) immunoprofile in hemangioblastoma: a helpful combination in the differential diagnosis with metastatic clear cell renal cell carcinoma to the central nervous system. Am J Surg Pathol 35(2):262–267
Doyle LA, Fletcher CD (2014) Peripheral hemangioblastoma: clinicopathologic characterization in a series of 22 cases. Am J Surg Pathol 38(1):119–127
Fan R (2014) PAX immunoreactivity in poorly differentiated small round cell tumors of childhood. Fetal Pediatr Pathol 33(4):244–252
Zhao M, Williamson SR, Yu J, Xia W, Li C, Zheng J, Zhu Y, Sun K, Wang Z, Cheng L (2013) PAX8 expression in sporadic hemangioblastoma of the kidney supports a primary renal cell lineage: implications for differential diagnosis. Hum Pathol 44(10):2247–2255
Surdez D, Benetkiewicz M, Perrin V, Han ZY, Pierron G, Ballet S, Lamoureux F, Rédini F, Decouvelaere AV, Daudigeos-Dubus E, Geoerger B, de Pinieux G, Delattre O, Tirode F (2012) Targeting the EWSR1-FLI1 oncogene-induced protein kinase PKC-β abolishes Ewing sarcoma growth. Cancer Res 72(17):4494–4503
Holmes BJ, Gown AM, Vang R, Ronnett BM, Yemelyanova A (2014) PAX8 expression in uterine malignant mesodermal mixed tumor (carcinosarcoma). Int J Gynecol Pathol 33(4):42–31
Sangoi AR, Cassarino DS (2013) PAX-8 expression in primary and metastatic Merkel cell carcinoma: an immunohistochemical analysis. Am J Dermatopathol 35(4):448–451
Morgan EA, Pozdnyakova O, Nascimento AF, Hirsch MS (2013) PAX8 and PAX5 are differentially expressed in B-cell and T-cell lymphomas. Histopathology 62(3):406–413
Fletcher CD, Bridge JA, Hogendoorn P, Mertens F (2013) WHO classification of tumours of soft tissue and bone. Fourth Edition. World Health Organization; 468 pp.
Bui MM, Han G, Geza A, Reed D, Gonzalez R, Pasha TL, Zhang P (2011) Connexin 43 is a prognostic biomarker for Ewing Sarcoma (EWS)/primitive neuroectodermal tumor (PNET). Sarcoma 2011:971050
Acknowledgments
We acknowledge Tingan Chen, MD, PhD; Agnieszka Kasprzak, MS; Joseph Johnson, MS from the Department of Analytic Microscopy Core H. Lee Moffitt Cancer Center and Research Institute and Sam D. Zeng, BS, MS-2 of Morsani College of medicine for their contribution in the technical aspect of this study. This project has been funded by the Department of Anatomic Pathology at Moffitt Cancer Center, Tampa, FL, USA.
Conflict of Interest
The authors report no conflicts of interest.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Markow, M., Bui, M.M., Lin, HY. et al. Evaluation of PAX8 Expression and Its Potential Diagnostic and Prognostic Value in Renal and Extra-Renal Ewing Sarcomas/PNETs. Pathol. Oncol. Res. 22, 115–120 (2016). https://doi.org/10.1007/s12253-015-9986-8
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12253-015-9986-8