Levels of angiogenesis and expression of angiogenesis‐related genes are prognostic for organ‐specific metastasis of renal cell carcinoma

Abstract

BACKGROUND.To identify organ-specific, metastasis-related factors that can be

Classification of renal cell carcinoma based on expression of VEGF and VEGF receptors in both tumor cells and endothelial cells

“…Smaller studies by others have shown variable associations between clinical outcome and microvessel density. 10,20 Kurban et al 6 showed that VHL mutations resulting in upregulation of HIF1a are associated with decreased microvessel density and low invasive potential, consistent with our results.…”

“…Other smaller studies assessing VEGF/VEGF-Rs and microvessel density have been conducted. [9][10][11] Jacobsen et al 12 assessed a relatively large cohort tissue microarray (TMA) for VEGF expression, but no assessment of VEGF-R expression and microvessel density was made. Our purpose was to assess expression of VEGF, VEGF-R1, VEGF-R2 and VEGF-R3 in three tissue components: RCC cells, endothelial cells and adjacent normal renal tissue on a large patient cohort with associated clinical/ pathological data.…”

Metastasis: cell-autonomous mechanisms versus contributions by the tumor microenvironment

“…Most, though not all, clinical studies demonstrate a direct correlation of high primary tumor blood microvessel densities (MVDs) with increased incidence of metastases [150,151]. Tumor MVD is a significant and independent prognostic indicator for relapse-free and overall survival of cancer patients [152].…”

Targeting fibroblast growth factor receptor (FGFR) pathway in renal cell carcinoma

“…[7] FGF/fibroblast growth factor receptor (FGFR) signaling promotes vascularization (vessel assembly, sprouting and branching), lymphangiogenesis and cellular growth in several human malignancies, [8][9][10] including RCC. [11] Interestingly, increased basic-FGF plasma concentrations correlate with high tumor grade and stage, [12] metastatic spreading [13] and poor prognosis [14] in kidney cancer patients. Moreover, FGF serum levels significantly increase in mRCC patients with disease progression while receiving sunitinib therapy, supporting the potential FGF-pathway role as a potent mediator of endothelial cell resistance to VEGFR inhibitors.…”