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Negative prognostic impact of PD-L1 expression in tumor cells of undifferentiated (anaplastic) carcinoma with osteoclast-like giant cells of the pancreas: study of 13 cases comparing ductal pancreatic carcinoma and review of the literature

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Abstract

Pancreatic carcinoma remains one of the leading cancer-related causes of death worldwide and is generally characterized by a dismal prognosis and limited potential for oncologic treatment. A rare subvariant of pancreatic cancer, undifferentiated carcinoma with osteoclast-like giant cells (UCOGC), has an unpredictable prognosis according to many previous studies, with unexpectedly long survival in individual cases. In this study, we collected, retrospectively, 13 cases of well-documented UCOGCs and performed immunohistochemistry focused on the expression of the programmed death-ligand 1 (PD-L1) and several other potential therapeutic and predictive markers (PanTRK, p53, MSH2, PMS2, and the number of tumor-infiltrating lymphocytes), to explore their correlation with the follow-up of the patients. As a control group, we examined 24 cases of conventional pancreatic ductal adenocarcinoma (PDAC). In our results, PanTRK was negative in all 24 cases. P53 did not show any significant differences between UCOGCs and PDACs, and the entire cohort was MSH2, MLH1, PMS2, and MSH6 positive. Significant differences were present in the analysis of PD-L1: UCOGCs were found to express PD-L1 significantly more frequently and have a higher number of tumor-infiltrating lymphocytes than PDAC. The expression of PD-L1 was related to significantly shorter survival in patients with UCOGC and in the entire cohort. Patients with PD-L1 negative UCOGCs displayed surprisingly long survival in comparison to PD-L1 positive UCOGCs and PDACs (both PD-L1+ and PD-L1−). We compared our results with previously published data, and, after statistical analysis, we were able to identify PD-L1 as an effective prognostic marker of UCOGC and suggest a strong need for a clinical trial of immune checkpoint immunotherapy in patients with advanced PD-L1 positive UCOGC.

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Acknowledgments

The authors thank Thomas Secrest for the revision of the English version of this article.

Funding

This work was supported by the Ministry of Health, Czech Republic (Conceptual development of research organization VFN64165, General University Hospital in Prague, and TN64190 Thomayer Hospital in Prague), by Charles University (Project Progress, Q28/LF1, and Q28/LF3 Oncology) and OPPK (Research Laboratory of Tumor Diseases, CZ.2.16/3.1.00/24509).

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Authors and Affiliations

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

    Jan Hrudka, Jana Moravcová & Radoslav Matěj

  2. Department of General Surgery, 3rd Faculty of Medicine, Charles University, University Hospital Kralovske Vinohrady, Prague, Czech Republic

    Kateřina Lawrie

  3. Department of Anesthesiology and Intensive Care, 3rd Faculty of Medicine, Charles University and Kralovske Vinohrady University Hospital, Prague, Czech Republic

    Petr Waldauf

  4. Institute of Pathology, 1st Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic

    Vanda Ciprová & Radoslav Matěj

  5. Clinical and Transplant Pathology Centre, Institute for Clinical and Experimental Medicine, Prague, Czech Republic

    Jana Moravcová

  6. Department of Pathology and Molecular Medicine, 3rd Faculty of Medicine, Charles University, Thomayer Hospital, Prague, Czech Republic

    Radoslav Matěj

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  1. Jan Hrudka
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  2. Kateřina Lawrie
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  3. Petr Waldauf
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  4. Vanda Ciprová
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  6. Radoslav Matěj
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Contributions

Jan Hrudka and Radoslav Matěj were the main contributors to the study conception and design. Material preparation and data collection were performed by Jan Hrudka, Kateřina Lawrie, Vanda Ciprová, and Jana Moravcová. Histopathological analysis was performed by Jan Hrudka and Radoslav Matěj. Statistical analysis was performed by Petr Waldauf. The first draft of the manuscript was written by Jan Hrudka, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Jan Hrudka.

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Hrudka, J., Lawrie, K., Waldauf, P. et al. Negative prognostic impact of PD-L1 expression in tumor cells of undifferentiated (anaplastic) carcinoma with osteoclast-like giant cells of the pancreas: study of 13 cases comparing ductal pancreatic carcinoma and review of the literature. Virchows Arch 477, 687–696 (2020). https://doi.org/10.1007/s00428-020-02830-8

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