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.

• MeSH
• Molecular Targeted Therapy methods   MeSH
• Adult MeSH
• Hypoxia-Inducible Factor 1, alpha Subunit metabolism   MeSH
• Phosphorylation MeSH
• Angiogenesis Inhibitors pharmacology   therapeutic use   MeSH
• Carcinoma, Renal Cell blood supply   drug therapy   metabolism   MeSH
• Middle Aged MeSH
• Humans MeSH
• Von Hippel-Lindau Tumor Suppressor Protein metabolism   MeSH
• Kidney Neoplasms blood supply   drug therapy   metabolism   MeSH
• Neovascularization, Pathologic drug therapy   genetics   MeSH
• Aged MeSH
• Signal Transduction drug effects   genetics   MeSH
• TOR Serine-Threonine Kinases metabolism   MeSH
• Basic Helix-Loop-Helix Transcription Factors metabolism   MeSH
• Vascular Endothelial Growth Factor A metabolism   MeSH
• Treatment Outcome MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Case Reports MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• endothelial PAS domain-containing protein 1 MeSH Browser
• Hypoxia-Inducible Factor 1, alpha Subunit MeSH
• HIF1A protein, human MeSH Browser
• Angiogenesis Inhibitors MeSH
• MTOR protein, human MeSH Browser
• Von Hippel-Lindau Tumor Suppressor Protein MeSH
• TOR Serine-Threonine Kinases MeSH
• Basic Helix-Loop-Helix Transcription Factors MeSH
• Vascular Endothelial Growth Factor A MeSH
• VEGFA protein, human MeSH Browser
• VHL protein, human MeSH Browser