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PD-L2: A prognostic marker in chromophobe renal cell carcinoma?

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Abstract

In the context of cancer immunotherapy, PD-1 as well as PD-L1 has been widely studied in renal cell carcinoma (RCC). PD-1 and PD-L1 play a significant role as prognostic markers in clear cell renal cell carcinoma. In contrast, little is known about PD-L2 expression patterns in RCC, especially in rarer subtypes. The aim of this study was to evaluate the prevalence, distribution and prognostic impact of PD-L2 expression in chromophobe (ch)RCC. Eighty-one patients who underwent renal surgery due to chRCC were retrospectively evaluated. Tumor specimens were analyzed for PD-L2 expression by immunohistochemistry. Expression data were associated with clinicopathological parameters and overall survival (OS). Twenty-three (28.4%) patients showed a PD-L2 > median (PD-L2 high) staining intensity. No significant association between clinicopathological parameters and PD-L2 expression was identified. A significant difference between 5- and 10-year OS in dependence of PD-L2 expression was found (PD-L2 low 96.4 and 87.7% vs. PD-L2 high 87.1 and 56%; log rank, p = 0.029). However, in multivariate analysis PD-L2 expression failed to be proofed as an independent prognostic factor. In conclusion, to our knowledge this is the first study evaluating the prognostic impact of PD-L2 in a considerably large cohort of chRCC. Our results showed a significant diminished OS in dependence of PD-L2 expression. This implicates that PD-L2 might play a role as prognostic marker in chRCC demanding further evaluation.

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Abbreviations

chRCC:

Chromophobe renal cell carcinoma

ccRCC:

Clear cell renal cell carcinoma

CD:

Cluster of differentiation

IHC:

Immunohistochemistry

LN:

Lymph node metastasis

OS:

Overall survival

PD-1:

Programmed death 1

PD-L1:

Programmed death ligand 1

PD-L2:

Programmed death ligand 2

RCC:

Renal cell carcinoma

TIMC:

Tumor-infiltrating mononuclear immune cells

TMA:

Tissue microarray

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Acknowledgements

The authors would like to thank Ulrike Muehlthaler for her assistance with the PD-L2 immunohistochemistry.

Funding

This work was supported by a grant from the Deutsche Forschungsgemeinschaft (DFG) (Grant No. ER 795/1-1, Franziska Erlmeier).

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Author notes

    Authors and Affiliations

    1. Institute of Pathology, Technical University Munich (TUM), Trogerstraße 18, 81675, Munich, Germany

      Franziska Erlmeier & Wilko Weichert

    2. Member of the German Renal Cell Tumor Consortium, Jena, Germany

      Franziska Erlmeier, Andres Jan Schrader, Arndt Hartmann & Sandra Steffens

    3. Member of the German Cancer Consortium (DKTK), Heidelberg, Germany

      Wilko Weichert

    4. Department of Urology, Technical University of Munich, Klinikum rechts der Isar, Munich, Germany

      Michael Autenrieth

    5. The Munich Cancer Registry of the Tumorzentrum Munich, Institute of Medical Information Processing, Biometry and Epidemiology, Ludwig-Maximilians-University Munich, Munich, Germany

      Max Wiedemann

    6. Clinic for Urology, University Hospital Muenster, Münster, Germany

      Andres Jan Schrader & Sandra Steffens

    7. Institute of Pathology, University Hospital of Erlangen, Erlangen, Germany

      Arndt Hartmann

    8. Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany

      Philipp Ivanyi

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    1. Franziska Erlmeier
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    Contributions

    FE, PI and SS participated in the data interpretation and drafting of the manuscript. PI and SS performed the statistical analysis. MW carried out clinical data acquisition. FE carried out the pathological data acquisition. WW, AH, MA and AJS contributed to data interpretation and revised the manuscript for important intellectual content. All authors read and approved the final manuscript.

    Corresponding author

    Correspondence to Franziska Erlmeier.

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    Conflict of interest

    The authors have declared no conflicts of interest.

    Ethical standards

    All procedures have been approved by the appropriate ethics committee and have therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. Informed consent was assessed prior to intervention. Analyses were performed in concordance with recommendations of the ethics commission of the Technical University of Munich and ethic comity approval (384/13). Details that disclose the identity of the subjects under study were omitted.

    Additional information

    Philipp Ivanyi and Sandra Steffens have contributed equally to this work.

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    Erlmeier, F., Weichert, W., Autenrieth, M. et al. PD-L2: A prognostic marker in chromophobe renal cell carcinoma?. Med Oncol 34, 71 (2017). https://doi.org/10.1007/s12032-017-0926-1

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    • DOI: https://doi.org/10.1007/s12032-017-0926-1

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