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Fibroblast growth factor receptor 4 (FGFR4) as detected by immunohistochemistry is associated with postoperative residual disease in ovarian cancer

  • Original Article – Cancer Research
  • Published:
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Abstract

Purpose

Fibroblast Growth Factor Receptor 4 (FGFR4) was proposed to hold prognostic significance in high-grade serous ovarian carcinoma (HGSOC). However, information on this deriving from large, representative patient panels is still missing, though such data would be indispensable to validate suitability of FGFR4 as prognostic marker or even pharmacological target.

Methods

1063 ovarian cancer cases were included in this study. Immunohistochemistry (IHC) was performed using two different anti-FGFR4 specific antibodies (HPA027273, sc-124) on an automated staining system. IHC data of both FGFR4 antibodies were available from 995 cases. FGFR4 immunostaining was correlated to prognostic factors including survival using uni- and multivariate proportional hazard models.

Results

FGFR4 was positively associated with advanced FIGO stage, high grade and presence of residual disease. When progression free (PFS) of FGFR4 negative vs. positive patients was compared, patients scored as FGFR4 positive had significantly shortened PFS as compared to those that stained negative. All associations of FGFR4 and shortened PFS were lost during multivariate testing. No significant associations were found in terms of OS.

Conclusions

We were not able to confirm FGFR4 as an independent negative prognosticator as described before. However, FGFR4 was highly prevalent in those cases harboring residual disease after debulking surgery. Since especially patients that could only be debulked sub-optimally may benefit from targeted adjuvant treatment, tyrosine kinase inhibitors targeting FGFRs might turn out to be an interesting future treatment option.

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Availability of data and material

The datasets used and/or analyzed during the current study available from the corresponding author on reasonable request.

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Funding

No specific funding was received.

Author information

Authors and Affiliations

  1. Department of Obstetrics and Gynecology, University of Heidelberg, Heidelberg, Germany

    Sabine Heublein

  2. Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, BC, Canada

    Michael S. Anglesio

  3. Department of Obstetrics and Gynecology, Mannheim University Hospital, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany

    Frederik Marmé

  4. Department of Obstetrics and Gynecology, University of Tuebingen, Tuebingen, Germany

    Stefan Kommoss

Authors
  1. Sabine Heublein
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  2. Michael S. Anglesio
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  3. Frederik Marmé
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  4. Stefan Kommoss
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Corresponding author

Correspondence to Frederik Marmé.

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Conflict of interest

Sabine Heublein received research support from Novartis, Ferring, Apceth and Addex; Honoria from Roche, travel expenses from Astra Zeneca. Frederik Marmé received honoraria from Roche, AstraZeneca, Pfizer, Clovis, Tesaro, Amgen, Celgene, Eisai, MSD, Genomic Health, Curevac; Travel expenses from Roche, Pfizer, Astra Zeneca, Pharma-Mar, Amgen, Celgene; Advisory Boards for Roche, Astra Zeneca, Pfizer, MSD, Amgen, Celgene, Genomic Health, Curevac. Stefan Kommoss and Michael S. Anglesio declare no competing interests.

Ethics approval

Collection of patient specimens and data from the British Columbia cohort was done under approved research protocols reviewed by the British Columbia Cancer Agency and University of British Columbia research ethics board (H05-60119).

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No written informed consent of the participants is needed given the circumstances described above.

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Frederik Marmé and Stefan Kommoss share senior authorship.

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Heublein, S., Anglesio, M.S., Marmé, F. et al. Fibroblast growth factor receptor 4 (FGFR4) as detected by immunohistochemistry is associated with postoperative residual disease in ovarian cancer. J Cancer Res Clin Oncol 145, 2251–2259 (2019). https://doi.org/10.1007/s00432-019-02986-0

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  • DOI: https://doi.org/10.1007/s00432-019-02986-0

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