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Tubulocystic renal cell carcinoma: is there a rational reason for targeted therapy using angiogenic inhibition? Analysis of seven cases

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Abstract

Generally, patients with renal cell carcinoma (RCC) are viewed as potential candidates for antiangiogenic targeted therapy. Tubulocystic RCC (TCRC) is a recently described entity which may behave aggressively, and the rationale for antiangiogenic therapy in this group of renal tumors has yet to be determined. Seven TCRCs and five non-tumor tissue samples from seven patients were subjected to relative expression analysis of mRNA levels of 16 genes involved in three angiogenic signal pathways: (1) VHL/HIF, (2) RTK/mitogen-activated protein kinase (MAPK), and (3) PI3K/Akt/mTOR. Two of them, pathways (2) and (3), are often targeted by antiangiogenic agents. We also determined the mutation and methylation status of the VHL gene. Finally, the levels of vascular endothelial growth factor A (VEGFA), HIF-1α, HIF-2α proteins, and phosphorylated mTOR protein were also determined. The comparison of tumor and control samples revealed no changes of mRNA levels of the following genes: VHL, HIF-1α, HIF-2α, PTEN, Akt2, Akt3, mTOR, VEGFA, KDR, HRas, C-Jun, EGFR, and FGF2. Significantly elevated mRNA level of TP53 was found, while the mRNA levels of FLT1 and C-FOS were reduced in tumor samples. No mutations or methylation in the VHL gene were found. Changes in levels of studied proteins VEGFA, HIF-1α, HIF-2α, and increased phosphorylation of mTOR protein were not found. Three studied angiogenic pathways (VHL/HIF, RTK/MAPK, and PI3K/Akt/mTOR) seem not to be upregulated in TCRC samples, so there appears to be no rationale for a general recommendation of antiangiogenic targeted therapeutic protocols for patients with these tumors.

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Acknowledgments

We thank Stanislav Kormunda for statistical analysis. The study was supported by Czech Government grant agency: IGA NT 12010–4.

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We declare that we have no conflict of interest.

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Authors and Affiliations

  1. Department of Pathology, Faculty of Medicine Plzen, Charles University Prague, Alej Svobody 80, 304 60, Pilsen, Czech Republic

    Petr Steiner, Jan Stehlik, Petr Martinek, Tomas Vanecek, Fredrik Petersson, Michal Michal, Marie Korabecna & Ondrej Hes

  2. Department of Urology, Faculty of Medicine Plzen, Charles University Prague, Alej Svobody 80, 304 60, Pilsen, Czech Republic

    Milan Hora & Ivan Travnicek

  3. Department of Pathology, National University Health System, 1E, Kent Ridge Road, Singapore, Singapore

    Fredrik Petersson

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  1. Petr Steiner
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Steiner, P., Hora, M., Stehlik, J. et al. Tubulocystic renal cell carcinoma: is there a rational reason for targeted therapy using angiogenic inhibition? Analysis of seven cases. Virchows Arch 462, 183–192 (2013). https://doi.org/10.1007/s00428-012-1367-z

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