c-Met in chromophobe renal cell carcinoma
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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.
KeywordsRenal cell carcinoma c-Met Epithelial-mesenchymal transition Chromophobe histology Chromophobe subtype Survival
Chromophobe renal cell carcinoma
Clear cell renal cell carcinoma
Circulating tumor cells
Hepatocyte growth/scatter factor
Lymph node metastasis
Mesenchymal-epithelial transition factor
Renal cell carcinoma
Vascular endothelial growth factor receptor
The authors would like to thank Ulrike Muehlthaler for her assistance with the c-Met immunohistochemistry.
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.
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).
Compliance with ethical standards
Conflict of interest
The authors have declared no conflicts of interest.
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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