PAX8 expression in anaplastic thyroid carcinoma is less than those reported in early studies: a multi-institutional study of 182 cases using the monoclonal antibody MRQ-50

  • Wei-An Lai
  • Jen-Fan HangEmail author
  • Chih-Yi Liu
  • Yanhua Bai
  • Zhiyan Liu
  • Haiyan Gu
  • SoonWon Hong
  • Ju Yeon Pyo
  • Chan Kwon Jung
  • Kennichi Kakudo
  • Andrey Bychkov
Original Article


Anaplastic thyroid carcinoma (ATC) is an aggressive malignant tumor composed of undifferentiated thyroid follicular cells. Pathological diagnosis of ATC can be challenging as the tumor may show morphological overlap with other neoplasms with anaplastic morphology. Immunohistochemical demonstration of thyroid origin facilitates the diagnosis of ATC. Previous studies using the polyclonal anti-PAX8 antibody 10336-1-AP suggested that PAX8 was the most sensitive marker, expressed in up to 80% of ATC. According to a 2018 NordiQC report, the monoclonal anti-PAX8 antibody MRQ-50 has become the most commonly used anti-PAX8 antibody worldwide. However, validation of this antibody in ATC is lacking. In this study, we recruited 182 ATC cases from seven institutions. Pathology slides were subjected to histology review. PAX8 immunohistochemistry using the MRQ-50 antibody was performed in whole tissue slides (n = 147) or tissue microarray sections (n = 35). We found PAX8 expression in 54.4% of the cases, which was significantly lower than those reported in prior studies with the polyclonal antibody. PAX8 expression was positively correlated with the presence of an epithelial pattern (63.6% vs 37.5%, p = 0.0008) and a coexisting differentiated thyroid carcinoma component (71.6% vs 44.3%, p = 0.0004), but was not associated with age, gender, specimen type, or presence of giant cell and sarcomatoid patterns. In conclusion, we demonstrated PAX8 expression using the monoclonal antibody MRQ-50 in only half of the cases in a large ATC series. Pathologists should be aware that PAX8 expression in ATC is less than those reported in early studies to avoid misdiagnosis.


Paired box gene 8 (PAX8) Anaplastic thyroid carcinoma (ATC) Undifferentiated thyroid carcinoma Immunohistochemistry MRQ-50 



A. Bychkov and J. Hang designed the study. W. Lai, J. Hang, C. Liu, Y. Bai, Z. Liu, H. Gu, S. Hong, J. Pyo, C. Jung, and A. Bychkov reviewed the slides and collected the data. W. Lai and J. Hang analyzed the data and performed the study. W. Lai, J. Hang, and A. Bychkov wrote the paper. K. Kakudo supervised the study and provided critical revision.

Funding information

This study was supported by the research grant from Taipei Veterans General Hospital, Taipei, Taiwan (Grant No.: V108B-011).

Compliance with ethical standards

This study was approved by the institutional review boards of the participating centers.

Conflict of interest

The authors declare that they have no conflict of interest.


  1. 1.
    Molinaro E, Romei C, Biagini A, Sabini E, Agate L, Mazzeo S, Materazzi G, Sellari-Franceschini S, Ribechini A, Torregrossa L, Basolo F, Vitti P, Elisei R (2017) Anaplastic thyroid carcinoma: from clinicopathology to genetics and advanced therapies. Nat Rev Endocrinol 13:644–660. CrossRefPubMedGoogle Scholar
  2. 2.
    Toner M, Banville N, Timon CI (2014) Laryngotracheal presentation of anaplastic thyroid carcinoma with squamous differentiation: seven cases demonstrating an under-recognized diagnostic pitfall. Histopathology 65:501–507. CrossRefPubMedGoogle Scholar
  3. 3.
    Ragazzi M, Ciarrocchi A, Sancisi V, Gandolfi G, Bisagni A, Piana S (2014) Update on anaplastic thyroid carcinoma: morphological, molecular, and genetic features of the most aggressive thyroid cancer. Int J Endocrinol. CrossRefGoogle Scholar
  4. 4.
    Bishop JA, Sharma R, Westra WH (2011) PAX8 immunostaining of anaplastic thyroid carcinoma: a reliable means of discerning thyroid origin for undifferentiated tumors of the head and neck. Hum Pathol 42:1873–1877. CrossRefPubMedGoogle Scholar
  5. 5.
    Rosai J, Kuhn E, Carcangiu ML (2006) Pitfalls in thyroid tumour pathology. Histopathology 49:107–120. CrossRefPubMedGoogle Scholar
  6. 6.
    Nonaka D, Tang Y, Chiriboga L, Rivera M, Ghossein R (2007) Diagnostic utility of thyroid transcription factors Pax8 and TTF-2 (FoxE1) in thyroid epithelial neoplasms. Mod Pathol 21:192–200. CrossRefPubMedGoogle Scholar
  7. 7.
    Ordonez NG, El-Naggar AK, Hickey RC, Samaan NA (1991) Anaplastic thyroid carcinoma. Immunocytochemical study of 32 cases. Am J Clin Pathol 96:15–24CrossRefGoogle Scholar
  8. 8.
    Higgins SE, Barletta JA (2018) Applications of immunohistochemistry to endocrine pathology. Adv Anat Pathol 25:413–429. CrossRefPubMedGoogle Scholar
  9. 9.
    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 35:816–826. CrossRefPubMedGoogle Scholar
  10. 10.
    Becker N, Chernock RD, Nussenbaum B, Lewis JSJ (2014) Prognostic significance of β-Human chorionic gonadotropin and PAX8 expression in anaplastic thyroid carcinoma. Thyroid 24:319–326. CrossRefPubMedGoogle Scholar
  11. 11.
    Suzuki A, Hirokawa M, Takada N, Higuchi M, Yamao N, Kuma S, Daa T, Miyauchi A (2015) Diagnostic significance of PAX8 in thyroid squamous cell carcinoma. Endocr J 62:991–995. CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Moretti L, Medeiros LJ, Kunkalla K, Williams MD, Singh RR, Vega F (2011) N-terminal PAX8 polyclonal antibody shows cross-reactivity with N-terminal region of PAX5 and is responsible for reports of PAX8 positivity in malignant lymphomas. Mod Pathol 25:231–236. CrossRefPubMedGoogle Scholar
  13. 13.
    Roge R, Nielsen O, Bzorek M, Nielsen S, Vyberg M (2018) NordiQC assessments of PAX8 immunoassays. Appl Immunohistochem Mol Morphol 26:221–224. CrossRefPubMedGoogle Scholar
  14. 14.
    Kuhn E, Ragazzi M, Ciarrocchi A, Torricelli F, de Biase D, Zanetti E, Bisagni A, Corrado S, Uccella S, La Rosa S, Bongiovanni M, Losito S, Piana S (2019) Angiosarcoma and anaplastic carcinoma of the thyroid are two distinct entities: a morphologic, immunohistochemical, and genetic study. Mod Pathol 32:787–798. CrossRefPubMedGoogle Scholar
  15. 15.
    Bychkov A, Kakudo K, Hong S (2017) Current practices of thyroid fine-needle aspiration in Asia: a missing voice. J Pathol Transl Med 51:517–520. CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Lloyd RV, Osamura RY, Klöppel G, Rosai J (2017) WHO classification of tumours of endocrine organs, 4th edn. International Agency for Research on Cancer, LyonGoogle Scholar
  17. 17.
    Kakudo K, Wakasa T, Ohta Y, Yane K, Ito Y, Yamashita H (2015) Prognostic classification of thyroid follicular cell tumors using Ki-67 labeling index: risk stratification of thyroid follicular cell carcinomas. Endocr J 62:1–12. CrossRefPubMedGoogle Scholar
  18. 18.
    Chernock RD (2016) Immunohistochemistry of thyroid gland carcinomas: clinical utility and diagnostic pitfalls. Diagn Histopathol (Oxf) 22:184–190. CrossRefGoogle Scholar
  19. 19.
    Nikiforov YE, Biddinger PW, Thompson LD (2012) Diagnostic pathology and molecular genetics of the thyroid: a comprehensive guide for practicing thyroid pathology. Lippincott Williams & Wilkins, PhiladelphiaGoogle Scholar
  20. 20.
    Ozcan A, Liles N, Coffey D, Shen SS, Truong LD (2011) PAX2 and PAX8 expression in primary and metastatic Müllerian epithelial tumors: a comprehensive comparison. Am J Surg Pathol 35:1837–1847. CrossRefPubMedGoogle Scholar
  21. 21.
    Ozcan A, Shen SS, Hamilton C, Anjana K, Coffey D, Krishnan B, Truong LD (2011) PAX8 expression in non-neoplastic tissues, primary tumors, and metastatic tumors: a comprehensive immunohistochemical study. Mod Pathol 24:751–764. CrossRefPubMedGoogle Scholar
  22. 22.
    Deeken-Draisey A, Yang G-Y, Gao J, Alexiev BA (2018) Anaplastic thyroid carcinoma: an epidemiologic, histologic, immunohistochemical, and molecular single-institution study. Hum Pathol 82:140–148. CrossRefPubMedGoogle Scholar
  23. 23.
    Liau J-Y, Tsai J-H, Jeng Y-M, Kuo K-T, Huang H-Y, Liang C-W, Yang C-Y (2016) The diagnostic utility of PAX8 for neuroendocrine tumors: an immunohistochemical reappraisal. Appl Immunohistochem Mol Morphol 24:57–63. CrossRefPubMedGoogle Scholar
  24. 24.
    Conant JL, DeSarno M, Ambaye AB, Bryant R, Zenali M (2016) PAX stains in hematologic malignancies, a diagnostic pitfall: a comparative study evaluating monoclonal PAX8s, polyclonal PAX2, and PAX5. J Hematop 9:53–58. CrossRefGoogle Scholar
  25. 25.
    Hubbard EW, Nodit L, Van Meter S (2016) Undifferentiated malignant neoplasm involving parotid and thyroid: sampling and PAX8 cross-reactivity can obscure the diagnosis of lymphoma. Case Rep Pathol 5. CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Wei-An Lai
    • 1
  • Jen-Fan Hang
    • 1
    • 2
    Email author
  • Chih-Yi Liu
    • 3
  • Yanhua Bai
    • 4
  • Zhiyan Liu
    • 5
    • 6
  • Haiyan Gu
    • 7
  • SoonWon Hong
    • 8
  • Ju Yeon Pyo
    • 8
  • Chan Kwon Jung
    • 9
  • Kennichi Kakudo
    • 10
  • Andrey Bychkov
    • 11
    • 12
    • 13
  1. 1.Department of Pathology and Laboratory MedicineTaipei Veterans General HospitalTaipeiTaiwan
  2. 2.School of MedicineNational Yang-Ming UniversityTaipeiTaiwan
  3. 3.Division of PathologySijhih Cathay General HospitalNew Taipei CityTaiwan
  4. 4.Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of PathologyPeking University Cancer Hospital & InstituteBeijingChina
  5. 5.Department of Pathology, School of Basic Medical SciencesShandong UniversityJinanChina
  6. 6.Department of Pathology, Qilu HospitalShandong UniversityJinanChina
  7. 7.Department of PathologyThe Affiliated Hospital of Qingdao UniversityQingdaoChina
  8. 8.Department of Pathology, College of Medicine, Gangnam Severance HospitalYonsei UniversitySeoulKorea
  9. 9.Department of Hospital Pathology, College of MedicineThe Catholic University of KoreaSeoulKorea
  10. 10.Department of Pathology, Nara Hospital, Faculty of MedicineKindai UniversityNaraJapan
  11. 11.Department of Pathology, Faculty of MedicineChulalongkorn UniversityBangkokThailand
  12. 12.Department of PathologyKameda Medical CenterKamogawaJapan
  13. 13.Department of Pathology, Graduate School of Biomedical SciencesNagasaki UniversityNagasakiJapan

Personalised recommendations