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.