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Annexin A10 optimally differentiates between intrahepatic cholangiocarcinoma and hepatic metastases of pancreatic ductal adenocarcinoma: a comparative study of immunohistochemical markers and panels

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Abstract

Discriminating intrahepatic cholangiocarcinoma (ICC) from hepatic metastases of pancreatic ductal adenocarcinoma (mPDAC) can be challenging. While pathologists might depend on clinical information regarding a primary tumor, their diagnosis will lead the patient either to potentially curative surgery (for ICC) or to palliation (for mPDAC). Beyond the validation of recently published potential biomarkers for PDAC (primary or metastatic) in a large cohort, we assessed diagnostic performance of the most promising candidates in the challenging task of discriminating metastatic PDAC (mPDAC) from ICC. In a training set of 87 ICC and 88 pPDAC, our previously identified biomarkers Annexin A1 (ANXA1), ANXA10, and ANXA13 were tested and compared with 11 published biomarkers or panels (MUCIN 1, Agrin, S100P, MUC5 AC, Laminin, VHL, CK 17, N-Cadherin, ELAC2, PODXL and HSPG2). Biomarkers with best results were further tested in an independent series of biopsies of 27 ICC and 36 mPDAC. Highest AUC values (between 0.72 and 0.84) for the discrimination between ICC and pPDAC were found in the training set for Annexin A1, Annexin A10, MUC5 AC, CK17, and N-Cadherin. These markers were further tested on an independent series of liver biopsies containing ICC or mPDAC. Diagnostic characteristics were evaluated for individual markers as well as for 3× panels. ANXA 10 showed the highest diagnostic potential of all single markers, correctly classifying 75% of mPDAC and 85% of ICC. Our results suggest that ANXA10 may be useful to differentiate between ICC and mPDAC, when only a tissue specimen is available.

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Acknowledgement

The authors thank Laura Malkus who provided expertise that greatly assisted the research.

Author information

Author notes

  1. Maike Ahrens and Hideo A. Baba contributed equally to the study.

Authors and Affiliations

  1. Institute of Pathology, University Hospital of Essen, University of Duisburg-Essen, Hufelandstr. 55, 45147, Essen, Germany

    Julia Kälsch, Stefanie Bertram, Leona L. Pott, Henning Reis, Daniela Westerwick, Christoph M. Schaefer, Dorothe Möllmann & Hideo A. Baba

  2. Department of Gastroenterology and Hepatology, University Hospital of Essen, University of Duisburg-Essen, Hufelandstr. 55, 45147, Essen, Germany

    Julia Kälsch, Jan-P. Sowa, Alexander Dechȇne & Ali Canbay

  3. Medizinisches Proteom-Center, Ruhr-Universität Bochum, Universitätsstr 150, 44780, Bochum, Germany

    Juliet Padden, Leona L. Pott, Barbara Sitek, Martin Eisenacher & Maike Ahrens

  4. Department of General, Visceral and Transplantation Surgery, University Hospital of Essen, University of Duisburg-Essen, Hufelandstr. 55, 45147, Essen, Germany

    Christian Fingas

Authors
  1. Julia Kälsch
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  2. Juliet Padden
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  3. Stefanie Bertram
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  4. Leona L. Pott
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  5. Henning Reis
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  8. Jan-P. Sowa
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  10. Christian Fingas
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  11. Alexander Dechȇne
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  12. Barbara Sitek
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  13. Martin Eisenacher
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  14. Ali Canbay
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  15. Maike Ahrens
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  16. Hideo A. Baba
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Corresponding author

Correspondence to Hideo A. Baba.

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Ethics Statement

The study protocol conforms to the ethical guidelines of the 1975 Declaration of Helsinki.

Conflict of interest

The authors declare that they have no conflict of interest.

Funding

This study was supported by PROFILE consortium Ruhr, European Regional Development Fund (ERDF) objective 2 “regional Competitiveness and Employment” 2007–2013 North-Rhine-Westphalia (Germany) and by the de.NBI project (FKZ 031 A 534A) of the Bundesministerium für Bildung und Forschung (BMBF). JK received intramural research funds of the Medical Faculty of the University of Duisburg-Essen (Interne Forschungsförderung Essen, IFORES).

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Kälsch, J., Padden, J., Bertram, S. et al. Annexin A10 optimally differentiates between intrahepatic cholangiocarcinoma and hepatic metastases of pancreatic ductal adenocarcinoma: a comparative study of immunohistochemical markers and panels. Virchows Arch 470, 537–543 (2017). https://doi.org/10.1007/s00428-017-2114-2

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  • DOI: https://doi.org/10.1007/s00428-017-2114-2

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