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c-Met in chromophobe renal cell carcinoma

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Abstract

c-Met plays a role as a prognostic marker in clear cell renal cell carcinoma. In addition, recently the tyrosine kinase inhibitor cabozantinib targeting c-Met was approved for the treatment of advanced renal cell carcinoma (RCC). In contrast to clear cell RCC, little is known about c-Met expression patterns in rarer RCC subtypes. The aim of this study was to evaluate the prevalence, distribution and prognostic impact of c-Met expression on chromophobe (ch)RCC. Patients who underwent renal surgery due to chRCC were retrospectively evaluated. Tumor specimens were analyzed for c-Met expression by immunohistochemistry. Expression data were associated with clinicopathological parameters including patient survival. Eighty-one chRCC patients were eligible for analysis. Twenty-four (29.6%) patients showed a high c-Met expression (c-Methigh, staining intensity higher than median). Our results showed an association between c-Methigh expression and the existence of lymph node metastasis (p = 0.007). No further significant clinicopathological associations with c-Met were identified, also regarding c-Met expression and overall survival. In conclusion, to our knowledge this is the first study evaluating the prognostic impact of c-Met in a considerably large cohort of chRCC. High c-Met expression is associated with the occurrence of lymph node metastasis. This indicates that c-Met might be implicated into metastatic progression in chRCC.

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Abbreviations

chRCC:

Chromophobe renal cell carcinoma

ccRCC:

Clear cell renal cell carcinoma

CTC:

Circulating tumor cells

EMT:

Epithelial-mesenchymal transition

HGF:

Hepatocyte growth/scatter factor

IHC:

Immunohistochemistry

LN:

Lymph node metastasis

Met:

Mesenchymal-epithelial transition factor

OS:

Overall survival

RCC:

Renal cell carcinoma

TMA:

Tissue microarray

VEGFR:

Vascular endothelial growth factor receptor

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Acknowledgements

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

Authors contribution

FE 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 PI contributed to data interpretation and revised the manuscript for important intellectual content. All authors read and approved the final manuscript.

Funding

This work was supported by a grant from the Deutsche Forschungsgemeinschaft (DFG) (Grant Number ER 795/1-1, Franziska Erlmeier) and by a grant from the Niedersächsische Krebsgesellschaft e.V. (Philipp Ivanyi and Sandra Steffens).

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    Authors and Affiliations

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

      Franziska Erlmeier & Wilko Weichert

    2. German Renal Cell Tumor Consortium, Jena, Germany

      Franziska Erlmeier, Arndt Hartmann & Sandra Steffens

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

      Philipp Ivanyi

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

      Arndt Hartmann

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

      Michael Autenrieth

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

      Max Wiedemann

    7. German Cancer Consortium (DKTK), Heidelberg, Germany

      Wilko Weichert

    8. Clinic for Urology, University Hospital Muenster, Muenster, Germany

      Sandra Steffens

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    1. Franziska Erlmeier
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    Correspondence to Franziska Erlmeier.

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    The authors have declared no conflicts of interest.

    Ethical standard

    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. Analyzes were performed in concordance with local ethic committee recommendations and ethic comity approval (384/13). Details that disclose the identity of the subjects under study were omitted.

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    Wilko Weichert and Sandra Steffens have contributed equally to this work.

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    Erlmeier, F., Ivanyi, P., Hartmann, A. et al. c-Met in chromophobe renal cell carcinoma. Med Oncol 34, 15 (2017). https://doi.org/10.1007/s12032-016-0874-1

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