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HER2 status as a potential predictive biomarker for ovarian clear cell carcinoma

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A COMMENTARY to this article was published on 24 October 2023

Abstract

Ovarian clear cell carcinoma (OCCC) is a subtype of ovarian carcinoma characterized by unique biological features and highly malignant characteristics including low chemosensitivity. Therefore, new therapeutic targets are needed. These could include the downstream pathways of receptor tyrosine kinases, especially the human epidermal growth factor receptor 2 (HER2). Our main objective was to characterize the HER2 status using immunohistochemistry (IHC) and FISH on 118 OCCCs, also considering the novel paradigm of HER2-zero and HER2-low status. Other aims included determination of the association between HER2 status and survival, HER2 gene DNA and RNA NGS analysis, HER2 gene expression analysis, and correlation between IHC and gene expression in HER2-zero and HER2-low cases. Cases with HER2 overexpression/amplification accounted for 5.1% (6/118), with additional 3% harbouring HER2 gene mutation. The remaining 112 (94.9%) cases were HER2-negative. Of these, 75% were classified as HER2-zero and 25% as HER2-low. This percentage of HER2 aberrations is significant concerning their possible therapeutic influence. Cases from the HER2-zero group showed significantly better survival. Although this relationship lost statistical significance in multivariate analysis, the results have potential therapeutic significance. HER2 gene expression analysis showed a significant correlation with HER2 IHC status in the entire cohort (HER2-positive vs. HER2-negative), while in the cohort of only HER2-negative cases, the results did not reach statistical significance, suggesting that gene expression analysis would not be suitable to confirm the subdivision into HER2-low and HER2-zero. Our results also emphasize the need for standardized HER2 testing in OCCC to determine the best predictor of clinical response.

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Data availability

The bioinformatics pipeline and module settings used during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

The authors thank Mr Zachary Harold Kane Kendall, BA (Institute for History of Medicine and Foreign Languages, First Faculty of Medicine, Charles University), for the English proofreading.

Funding

This work was supported by the Ministry of Health, Czech Republic (RVO VFN 64165 and AZV NV19-03–00007), by Charles University (Project UNCE204065, SVV260516), and by the European Regional Development Fund (EF16_013/0001674) and BBMRI_CZ LM2023033.

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Authors and Affiliations

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

    Michaela Kendall Bártů, Kristýna Němejcová, Romana Michálková, Ivana Stružinská, Nikola Hájková, Jan Hojný, Eva Krkavcová, Radoslav Matěj & Pavel Dundr

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

    Jan Laco

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

    Radoslav Matěj & Jana Drozenová

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

    Radoslav Matěj

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

    Gábor Méhes

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

    Pavel Fabian

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

    Jitka Hausnerová

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

    Marián Švajdler

  9. Department of Pathology and Molecular Medicine, Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Prague, Czech Republic

    Petr Škapa

  10. Department of Obstetrics and Gynecology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic

    David Cibula

  11. Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic

    Tomáš Zima

Authors
  1. Michaela Kendall Bártů
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  2. Kristýna Němejcová
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  3. Romana Michálková
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  4. Ivana Stružinská
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  5. Nikola Hájková
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  6. Jan Hojný
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  7. Eva Krkavcová
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  8. Jan Laco
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  9. Radoslav Matěj
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  10. Jana Drozenová
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  11. Gábor Méhes
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  12. Pavel Fabian
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  13. Jitka Hausnerová
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  14. Marián Švajdler
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  15. Petr Škapa
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  16. David Cibula
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  17. Tomáš Zima
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  18. Pavel Dundr
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Contributions

All authors contributed to the study conception and design. Michaela Kendall Bártů and Pavel Dundr conceived the study and carried out experiments, Kristýna Němejcová has participated in the assessment of the immunohistochemistry results and the FISH analyses. Ivana Stružinská, Jan Hojný, Nikola Hájková, and Pavel Dundr conceived experiments and analysed data. Romana Michálková performed the statistical analyses. Eva Krkavcová carried out the molecular genetics part of the experiments. Jan Laco, Radoslav Matěj, Jana Drozenová, Gábor Méhes, Pavel Fabian, Jitka Hausnerová, Marián Švajdler, Petr Škapa, David Cibula, and Tomáš Zima participated in the selection and evaluation of cases, provided the clinical data and participated in the data analysis. All authors were involved in writing the paper and had final approval of the submitted and published versions.

Corresponding author

Correspondence to Michaela Kendall Bártů.

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Ethics approval and consent to participate

The study has been approved by the Ethics Committee of the General University Hospital in Prague in compliance with the Helsinki Declaration. The Ethics Committee did not require the procurement of informed consent, given that according to the Czech Law (Act. no. 373/11, and its amendment Act no. 202/17) it is not necessary to provide informed consent in fully anonymized studies.

Conflict of interest

The authors declare no competing interests.

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Kendall Bártů, M., Němejcová, K., Michálková, R. et al. HER2 status as a potential predictive biomarker for ovarian clear cell carcinoma. Virchows Arch 483, 497–507 (2023). https://doi.org/10.1007/s00428-023-03640-4

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