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Tubulocystic renal cell carcinoma: is there a rational reason for targeted therapy using angiogenic inhibition? Analysis of seven cases.
MedLine Citation:
PMID:  23296808     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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.
Authors:
Petr Steiner; Milan Hora; Jan Stehlik; Petr Martinek; Tomas Vanecek; Fredrik Petersson; Michal Michal; Marie Korabecna; Ivan Travnicek; Ondrej Hes
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-8
Journal Detail:
Title:  Virchows Archiv : an international journal of pathology     Volume:  -     ISSN:  1432-2307     ISO Abbreviation:  Virchows Arch.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-8     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9423843     Medline TA:  Virchows Arch     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Department of Pathology, Faculty of Medicine Plzen, Charles University Prague, Alej Svobody 80, 304 60, Pilsen, Czech Republic.
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