Clinical Significance of Tumor Angiogenesis in Patients with Localized Renal Cell Carcinoma

Nativ, Ofer; Sabo, Edmond; Reiss, Ari; Wald, Moshe; Madjar, Shahar; Moskovitz, Boaz

doi:10.1016/s0090-4295(98)00019-3

Cited by 79 publications

(63 citation statements)

References 20 publications

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“…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.…”

Section: Discussionsupporting

confidence: 91%

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

Kluger

Siddiqui

Angeletti

et al. 2008

Laboratory Investigation

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Section: Discussionsupporting

confidence: 91%

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

Kluger

Siddiqui

Angeletti

et al. 2008

Laboratory Investigation

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“…An interesting observation is that Lim1 silencing in tumors of human CCC-bearing nude mice did not affect tumor vascularization. It should be noted, however, that reports dealing with the prognostic value of vascularisation in human CCC have shown either no effect on patient survival, better survival, or worse prognosis (MacLennan and Bostwick, 1995;Nativ et al, 1998;Imao et al, 2004;Yao et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

LIM-class homeobox gene Lim1, a novel oncogene in human renal cell carcinoma

et al. 2010

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“…In earlier studies, MVD was used as a parameter for angiogenesis in RCC and evaluated as a possible prognostic marker, however leading to conflicting results Nativ et al, 1998;Rioux-Leclercq et al, 2001;Sabo et al, 2001). To our knowledge, this is the first study in which the fraction of proliferating ECs (ECP%) is investigated within RCC.…”

Section: Discussionmentioning

confidence: 99%

High-grade clear cell renal cell carcinoma has a higher angiogenic activity than low-grade renal cell carcinoma based on histomorphological quantification and qRT–PCR mRNA expression profile

et al. 2007

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Clear cell renal cell carcinoma (CC-RCC) is a highly vascularised tumour and is therefore an attractive disease to study angiogenesis and to test novel angiogenesis inhibitors in early clinical development. Endothelial cell proliferation plays a pivotal role in the process of angiogenesis. The aim of this study was to compare angiogenesis parameters in low nuclear grade (n ¼ 87) vs high nuclear grade CC-RCC (n ¼ 63). A panel of antibodies was used for immunohistochemistry: CD34/Ki-67, carbonic anhydrase IX, hypoxia-inducible factor-1a (HIF-1a) and vascular endothelial growth factor (VEGF). Vessel density (MVD -microvessel density), endothelial cell proliferation fraction (ECP%) and tumour cell proliferation fraction (TCP%) were assessed. mRNA expression levels of angiogenesis stimulators and inhibitors were determined by quantitative RT -PCR. High-grade CC-RCC showed a higher ECP% (P ¼ 0.049), a higher TCP% (P ¼ 0.009), a higher VEGF protein expression (Po0.001), a lower MVD (Po 0.001) and a lower HIF-1a protein expression (P ¼ 0.002) than low-grade CC-RCC. Growth factor mRNA expression analyses revealed a higher expression of angiopoietin 2 in low-grade CC-RCC. Microvessel density and ECP% were inversely correlated (Rho ¼ À0.26, P ¼ 0.001). Because of the imperfect association of nuclear grade and ECP% or MVD, CC-RCC was also grouped based on low/high MVD and ECP%. This analysis revealed a higher expression of vessel maturation and stabilisation factors (placental growth factor, PDGFB1, angiopoietin 1) in CC-RCC with high MVD, a group of CC-RCC highly enriched in low nuclear grade CC-RCC, with low ECP%. Our results suggest heterogeneity in angiogenic activity and vessel maturation of CC-RCC, to a large extent linked to nuclear grade, and, with probable therapeutic implications.

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Clinical Significance of Tumor Angiogenesis in Patients with Localized Renal Cell Carcinoma

Cited by 79 publications

References 20 publications

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

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

LIM-class homeobox gene Lim1, a novel oncogene in human renal cell carcinoma

High-grade clear cell renal cell carcinoma has a higher angiogenic activity than low-grade renal cell carcinoma based on histomorphological quantification and qRT–PCR mRNA expression profile

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