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Reduced MFAP5 expression in stroma of gallbladder adenocarcinoma and its potential diagnostic utility

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Abstract

The diagnosis of invasive adenocarcinoma of the gallbladder can sometimes be challenging. The presence of true desmoplastic reaction facilitates the diagnosis of invasion. However, desmoplasia-like changes can be observed in benign gallbladder conditions, and recognition of desmoplasia may be challenging based on morphology. In this study, we tested the expression pattern of microfibril-associated protein 5 (MFAP5), a promising immunohistochemical marker for desmoplasia, in benign gallbladders with desmoplasia-like reaction and gallbladders with invasive adenocarcinoma. We also evaluated the diagnostic utility of MFAP5 in challenging cases with an interobserver agreement study. The results showed that all benign cases retained intact/positive MFAP5 staining pattern in periglandular connective tissue, whereas 79.3% (23 out of 29) of cases of adenocarcinomas demonstrated diffuse and complete loss of MFAP5 staining in the tumor stroma. Interobserver agreement was improved by 2.66 times when images of MFAP5 immunohistochemistry were provided. In conclusion, MFAP5 expression is downregulated in the desmoplastic stroma of gallbladder adenocarcinoma and may provide a useful diagnostic marker in difficult cases.

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Data availability

The data that support the findings of this study are available from the corresponding author, XZ, upon reasonable request.

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This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Authors and Affiliations

  1. Department of Pathology, Brigham and Women’s Hospital, Boston, MA, USA

    Lei Zhao

  2. Department of Pathology, St. Luke’s University Health Network, Bethlehem, PA, USA

    Liyan Xu

  3. Department of Pathology, Foundation Medicine, Inc., Morrisville, NC, USA

    Amanda Hemmerich & N. Lynn Ferguson

  4. Department of Pathology, Duke University Medical Center, Durham, NC, USA

    Cynthia D. Guy, Shannon J. McCall, Diana M. Cardona & Xuefeng Zhang

  5. Department of Pathology, University of Michigan, Ann Arbor, MI, USA

    Maria Westerhoff

  6. Department of Pathology, Mayo Clinic, Scottsdale, AZ, USA

    Rish K. Pai

  7. Department of Pathology, The University of Chicago, Chicago, IL, USA

    Shu-Yuan Xiao & John Hart

  8. Department of Biostatistics and Bioinformatics, Duke University School of Medicine, Durham, NC, USA

    Beiyu Liu & Cynthia L. Green

  9. Department of Anatomic Pathology, Cleveland Clinic, Cleveland, OH, USA

    Xuefeng Zhang

Authors
  1. Lei Zhao
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  2. Liyan Xu
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  14. Xuefeng Zhang
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Contributions

Conceptualization, Xuefeng Zhang; methodology, Lei Zhao, Liyan Xu, and Xuefeng Zhang; data generation and collection, Lei Zhao, Liyan Xu, Amanda Hemmerich, N. Lynn Ferguson, Cynthia D. Guy, Shannon J. McCall, Diana M. Cardona, Maria Westerhoff, Rish K. Pai, Shu-Yuan Xiao, John Hart, and Xuefeng Zhang; statistical analysis, Beiyu Liu and Cynthia L. Green; writing and original draft preparation, Lei Zhao and Xuefeng Zhang; writing, review, and editing, all authors.

Corresponding author

Correspondence to Xuefeng Zhang.

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The authors declare that they have no conflict of interest.

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This study was approved by the Institutional Review Board with waiver of informed consent.

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Parts of this study have been presented as an abstract at the United States and Canadian Academy of Pathology 2018 Annual Meeting.

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Zhao, L., Xu, L., Hemmerich, A. et al. Reduced MFAP5 expression in stroma of gallbladder adenocarcinoma and its potential diagnostic utility. Virchows Arch 478, 427–434 (2021). https://doi.org/10.1007/s00428-020-02925-2

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  • DOI: https://doi.org/10.1007/s00428-020-02925-2

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