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An extensive immunohistochemical analysis of 290 ovarian adult granulosa cell tumors with 29 markers

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Abstract

The current knowledge about the immunohistochemical features of adult granulosa cell tumor (AGCT) is mostly limited to the “traditional” immunohistochemical markers of sex cord differentiation, such as inhibin, calretinin, FOXL2, SF1, and CD99. Knowledge about the immunohistochemical markers possibly used for predictive purpose is limited. In our study, we focused on the immunohistochemical examination of 290 cases of AGCT classified based on strict diagnostic criteria, including molecular testing. The antibodies used included 12 of the “diagnostic” antibodies already examined in previous studies, 10 antibodies whose expression has not yet been examined in AGCT, and 7 antibodies with possible predictive significance, including the expression of HER2, PD-L1, CTLA4, and 4 mismatch repair (MMR) proteins. The results of our study showed expression of FOXL2, SF1, CD99, inhibin A, calretinin, ER, PR, AR, CKAE1/3, and CAIX in 98%, 100%, 90%, 78%, 45%, 41%, 94%, 82%, 26%, and 9% of AGCT, respectively. GATA3, SATB2, napsin A, MUC4, TTF1, and CD44 were all negative. PTEN showed a loss of expression in 71% of cases and DPC4 in 4% of cases. The aberrant staining pattern (overexpression) of p53 was found in 1% (3/268) of cases, 2 primary tumors, and 1 recurrent case. Concerning the predictive markers, the results of our study showed that AGCT is microsatellite stable, do not express PD-L1, and are HER2 negative. The CTLA4 expression was found in almost 70% of AGCT tumor cells.

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Acknowledgements

The authors wish to extend their gratitude to Mgr. Zachary H. K. Kendall, B.A. (Institute for History of Medicine and Foreign Languages, First Faculty of Medicine, Charles University in Prague) for the English language editing.

Funding

This work was supported by the Ministry of Health, Czech Republic (MH CZ DRO-VFN 64165 and AZV NU21-03–00238), by Charles University (Project UNCE24/MED/018, SVV 260631), and by the European Regional Development Fund (EF16_013/0001674 and BBMRI_CZ LM2023033).

Author information

Authors and Affiliations

  1. Department of Pathology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Studničkova 2, 12800, Prague 2, Czech Republic

    Kristýna Němejcová, Adam Šafanda, Michaela Kendall Bártů, Romana Michálková, Radoslav Matěj & Pavel Dundr

  2. Šikl’s Department of Pathology, The Faculty of Medicine and Faculty Hospital in Pilsen, Charles University, Pilsen, Czech Republic

    Marián Švajdler

  3. Department of Oncological Pathology, Masaryk Memorial Cancer Institute, Brno, Czech Republic

    Tetiana Shatokhina

  4. The Fingerland Department of Pathology, Charles University Faculty of Medicine in Hradec Králové and University Hospital Hradec Králové, Charles University, Prague, Czech Republic

    Jan Laco

  5. Department of Pathology, 3rd Faculty of Medicine, Charles University, University Hospital Královské Vinohrady, 10034, Prague, Czech Republic

    Radoslav Matěj & Jana Drozenová

  6. Department of Pathology and Molecular Medicine, Third Faculty of Medicine, Charles University, Thomayer University Hospital, Prague, Czech Republic

    Radoslav Matěj

  7. Department of Pathology, Faculty of Medicine, University of Debrecen, 4032, Debrecen, Hungary

    Gábor Méhes

  8. Department of Pathology, University Hospital Brno and Medical Faculty, Masaryk University, Brno, Czech Republic

    Jitka Hausnerová

  9. Department of Pathology, Bulovka University Hospital, Prague, Czech Republic

    Zuzana Špůrková

  10. Division of Gynecologic Oncology, Department of Surgical Oncology, Masaryk Memorial Cancer Institute and Medical Faculty of Masaryk University, Brno, Czech Republic

    Monika Náležinská

Authors
  1. Kristýna Němejcová
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  2. Adam Šafanda
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  3. Michaela Kendall Bártů
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  4. Romana Michálková
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  5. Marián Švajdler
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  6. Tetiana Shatokhina
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  7. Jan Laco
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  8. Radoslav Matěj
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  9. Gábor Méhes
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  10. Jana Drozenová
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  11. Jitka Hausnerová
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  12. Zuzana Špůrková
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  13. Monika Náležinská
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  14. Pavel Dundr
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Contributions

KN and PD drew up the study concept and design. All authors participated on material preparation, data collection, and/or analyses. The first draft of the manuscript was written by KN. All authors commented on previous versions of the manuscript and approved the final manuscript.

Corresponding author

Correspondence to Kristýna Němejcová.

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Ethical approval

The study was approved by the Ethics Committee of the General University Hospital in Prague in compliance with the Helsinki Declaration (No. 2140/19 S-IV). The Ethics Committee waived the requirement for informed consent as according to the Czech Law (Act. no. 373/11, and its amendment Act no. 202/17), it is not necessary to obtain informed consent in fully anonymized studies.

Informed consent

Not applicable.

Competing interests

The authors declare no competing interests.

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Němejcová, K., Šafanda, A., Kendall Bártů, M. et al. An extensive immunohistochemical analysis of 290 ovarian adult granulosa cell tumors with 29 markers. Virchows Arch (2024). https://doi.org/10.1007/s00428-024-03854-0

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