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FGFR2-IIIb Expression by Immunohistochemistry Has High Specificity in Cholangiocarcinoma with FGFR2 Genomic Alterations

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Abstract

Background

FGFR2 genomic alterations are observed in 10–20% of cholangiocarcinoma (CCA). Although FGFR2 fusions are an important actionable target, FGFR2 protein expression has not been thoroughly characterized.

Aims

To evaluate FGFR2 protein expression in cholangiocarcinoma harboring FGFR2 genomic alterations.

Methods

FGFR2 protein expression was evaluated in 99 CCA cases with two different antibodies. FGFR2 genomic alterations were confirmed via next-generating sequencing (NGS) or FISH. Primary objective was to determine the specificity and sensitivity of FGFR2 immunohistochemistry staining for detecting FGFR2 genomic alterations. Secondary objectives included overall FGFR2 immunohistochemistry staining in CCA patients, and evaluation of whether FGFR2 expression correlates with clinical outcomes including overall survival (OS), progression-free survival (PFS), and time-to-tumor recurrence (TTR).

Results

Immunohistochemistry staining with two antibodies against FGFR2, FPR2-D, and clone 98706 showed high accuracy (78.7% and 91.9%) and specificity (82.9% and 97.7%), and moderate sensitivity (53.9% and 57.1%), respectively, when compared with the standard methods for detecting FGFR2 genomic alterations. In a median follow-up of 72 months, there were no statistically significant differences in OS, PFS, and TTR, for patients with positive or negative FGFR2 staining.

Conclusion

FGFR2 protein expression by immunohistochemistry has high specificity and therefore could be used to imply the presence of FGFR2 genomic alterations in the context of a positive test. In the case of a negative test, NGS or FISH would be necessary to ascertain cases with FGFR2 genomic alterations.

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Acknowledgments

This work was supported by the National Institute of Health (NIH) through a DP2 Award CA195764 (to MJB); National Cancer Institute (NCI) K12 award CA090628 (to MJB), SPORE Project Award 5P50CA210964-03 (to GJG and MJB), SPORE Supplement Award 3P50CA210964-02S1 (to OB), K01 award CA234324 (to BN), Mayo Clinic Center for Individualized Medicine (CIM) Precision Cancer Therapeutics Program; and Mayo Clinic Cancer Center. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH.

Author information

Author notes

  1. Pedro Luiz Serrano Uson Junior and Thomas T. DeLeon have contributed equally to this work.

Authors and Affiliations

  1. Division of Hematology and Oncology, Department of Medicine, Mayo Clinic, Scottsdale, AZ, USA

    Pedro Luiz Serrano Uson Junior, Thomas T. DeLeon, James M. Bogenberger, Daniel H. Ahn, Mohammad Bassam Sonbol, Tanios Bekaii-Saab, Alexander T. Baker, Oumar Barro, Chelsae Dumbauld, Yumei Zhou, Nathalie Meurice, Mansi Arora, Joachim Petit, Natalie Elliott, Bolni Nagalo & Mitesh J. Borad

  2. Division of Anatomic Pathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Scottsdale, AZ, USA

    Rish K. Pai & Marcela A. Salomao

  3. Department of Health Sciences Research, Section of Biostatistics, Mayo Clinic, Scottsdale, AZ, USA

    Heidi E. Kosiorek

  4. Division of Medical Oncology, Mayo Clinic, Rochester, MN, USA

    Aaron S. Mansfield, Rory Smoot & Amit Mahipal

  5. Arizona State University, Tempe, AZ, USA

    Kenneth Buetow & Bertram Jacobs

  6. Division of Gastroenterology and Hepatology, Department of Internal Medicine, Rochester, MN, USA

    Gregory J. Gores

  7. Department of Molecular Medicine, Rochester, MN, USA

    George Vasmatzis & Mitesh J. Borad

  8. Division of Anatomic Pathology and Laboratory Medicine, Department of Pathology, Mayo Clinic, Rochester, MN, USA

    Benjamin R. Kipp

  9. Mayo Clinic School of Medicine, Scottsdale, AZ, USA

    Faaiq N. Aslam

  10. Center for Individualized Medicine, Mayo Clinic, Rochester, MN, USA

    Aaron S. Mansfield, Michael Barrett & Mitesh J. Borad

  11. Mayo Clinic Cancer Center, 5777 E Mayo Blvd, Phoenix, AZ, USA

    Mitesh J. Borad

  12. Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR, USA

    Bolni Nagalo

  13. Hospital Israelita Albert Einstein, São Paulo, SP, Brazil

    Pedro Luiz Serrano Uson Junior

  14. Division of Clinical Trials and Biostatistics, Mayo Clinic, Rochester, MN, USA

    Jun Yin

  15. Division of Hematology/Oncology, Mayo Clinic, Jacksonville, FL, USA

    Hani Babiker

Authors
  1. Pedro Luiz Serrano Uson Junior
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  2. Thomas T. DeLeon
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  31. Mitesh J. Borad
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Corresponding author

Correspondence to Mitesh J. Borad.

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Conflict of interest

This study was done in collaboration with Five Prime Therapeutics Inc. MJB has received grant to institution from Senhwa Pharmaceuticals, Adaptimmune, Agios Pharmaceuticals, Halozyme Pharmaceuticals, Five Prime Pharmaceuticals, Celgene Pharmaceuticals, EMD Merck Serono, Toray, Dicerna, Taiho Pharmaceuticals, Sun Biopharma, Isis Pharmaceuticals, Redhill Pharmaceuticals, Boston Biomed, Basilea, Incyte Pharmaceuticals, Mirna Pharmaceuticals, Medimmune, Bioline, Sillajen, ARIAD Pharmaceuticals, PUMA Pharmaceuticals, Novartis Pharmaceuticals, QED Pharmaceuticals, Pieris Pharmaceuticals, consultancy from ADC Therapeutics, Exelixis Pharmaceuticals, Inspyr Therapeutics, G1 Therapeutics, Immunovative Therapies, OncBioMune Pharmaceuticals, Western Oncolytics, Lynx Group, and travel support from Astra Zeneca. JMB and MJB have received bemarituzumab under a Material Transfer Agreement with Five Prime Therapeutics Inc. to facilitate ongoing preclinical studies. The remaining authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript.

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Uson Junior, P.L.S., DeLeon, T.T., Bogenberger, J.M. et al. FGFR2-IIIb Expression by Immunohistochemistry Has High Specificity in Cholangiocarcinoma with FGFR2 Genomic Alterations. Dig Dis Sci 67, 3797–3805 (2022). https://doi.org/10.1007/s10620-021-07303-9

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