Prognostic significance of vascular endothelial growth factor expression in clear cell renal cell carcinoma

Djordjević, Gordana; Mozetič, Vladimir; Mozetić, Danijela Vrdoljak; Licul, Vanja; Matušan-Ilijaš, Koviljka; Mustać, Elvira; Oguić, Romano; Fučkar, Željko; Jonjić, Nives

doi:10.1016/j.prp.2006.12.002

Cited by 30 publications

(25 citation statements)

References 27 publications

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“…Besides, our study offered more information on VEGF staining pattern and differences between CCRCCs and non-CCRCCs. There was a higher heterogeneity in protein and mo- lecular VEGF expression in CCRCCs than in non-CCRCCs, which is in accordance with previous findings that CCRCCs and nonCCRCCs behave differently (20)(21)(22).…”

Section: Discussionsupporting

confidence: 91%

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Relationship Between Vascular Endothelial Growth Factor and Nuclear Factor-κB in Renal Cell Tumors

et al. 2008

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Aim To assess the relationship between protein and messenger RNA (mRNA) levels of vascular endothelial growth factor (VEGF) and subcellular localization of nuclear factor-kappa B (NF-κB), proliferation rate of tumor cells, and clinicopathological characteristics of renal cell tumors.Methods We analyzed 31 one renal cell tumors -22 clear cell renal cell carcinomas (CCRCC) and 9 other histologic types (non-CCRCC). VEGF expression and subcellular localization of p65 member of NF-κB and Ki67 were immunohistochemically evaluated for the proliferation rate of tumor cells. Expression of VEGF mRNA was assessed using quantitative real-time polymerase chain reaction after total RNA extraction from snap-frozen tumor tissue samples.Results Cytoplasmic localization of VEGF protein in renal cell tumors showed a perimembranous and diffuse pattern, the former being more evident in CCRCC (27.1 ± 18.9 vs 3.3 ± 10 % tumors, P<0.001) and the latter in non-CCRCC type (71.7 ± 23.2 vs 31.1 ± 22.1 % tumors, P < 0.001). Heterogeneity in VEGF gene expression was more pronounced in CCRCC type than in non-CCRCC type (P = 0.004). In addition, perimembranous VEGF pattern was associated with higher VEGF mRNA levels (P = 0.006) and diffuse VEGF pattern with lower VEGF mRNA levels (P < 0.001). Nuclear and cytoplasmic staining of NF-κB/ p65 was observed in the majority of tumor cells. A significant association was recorded between cytoplasmic NK-κB/65 staining and VEGF staining of diffuse pattern (P = 0.026). Association between NF-κB/65 and proliferation rate of tumor cells was significant for cytoplasmic staining (P = 0.039) but not for nuclear NFkB/p65 staining (P = 0.099). ConclusionHigher but inhomogeneous expression of VEGF in tumor cells, especially in CCRCCs, is associated with NF-κB/65 activity. This indicates that both VEGF and NF-κB/65 may be important in renal carcinogenesis, representing a possible molecular target in the treatment of renal cell carcinoma.

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Section: Discussionsupporting

confidence: 91%

“…We have already reported on the association we found between diffuse cytoplasmic staining and lower degree of vascularization and between perimembranous staining and higher degree of vascularization (22). The present study showed the up-regulation of mRNA VEGF only in renal cell tumors with perimembranous VEGF expression.…”

Section: Discussionsupporting

confidence: 75%

Relationship Between Vascular Endothelial Growth Factor and Nuclear Factor-κB in Renal Cell Tumors

et al. 2008

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“…A possible reason for this is the strong association we observed among retroperitoneal collaterals and necrosis and high-grade ccRCC and the fact that all ccRCCs with necrosis had retroperitoneal collaterals. We hypothesize that the presence of central necrosis and extensive retroperitoneal collaterals on MR imaging are macroscopic manifestations of the intense angiogenic process occurring in high-grade ccRCCs [32,33] and will indicate a more aggressive biologic behavior [34,35].…”

Section: Discussionmentioning

confidence: 99%

MR classification of renal masses with pathologic correlation

et al. 2007

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To perform a feature analysis of malignant renal tumors evaluated with magnetic resonance (MR) imaging and to investigate the correlation between MR imaging features and histopathological findings. MR examinations in 79 malignant renal masses were retrospectively evaluated, and a feature analysis was performed. Each renal mass was assigned to one of eight categories from a proposed MRI classification system. The sensitivity and specificity of the MRI classification system to predict the histologic subtype and nuclear grade was calculated. Subvoxel fat on chemical shift imaging correlated to clear cell type (p < 0.05); sensitivity = 42%, specificity = 100%. Large size, intratumoral necrosis, retroperitoneal vascular collaterals, and renal vein thrombosis predicted high-grade clear cell type (p < 0.05). Small size, peripheral location, low intratumoral SI on T2-weighted images, and low-level enhancement were associated with low-grade papillary carcinomas (p < 0.05). The sensitivity and specificity of the MRI classification system for diagnosing low grade clear cell, high-grade clear cell, all clear cell, all papillary, and transitional carcinomas were 50% and 94%, 93% and 75%, 92% and 83%, 80% and 94%, and 100% and 99%, respectively. The MRI feature analysis and proposed classification system help predict the histological type and nuclear grade of renal masses.

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“…VEGF may play a role in promoting tumor growth and metastasis by participating in both paracrine and autocrine pathways [8]. In clear-cell renal cell carcinoma, overexpression of VEGF as demonstrated on histologic section, is associated with poor prognosis [9].…”

Section: Introductionmentioning

confidence: 99%

The inhibition of Endostar on the angiogenesis and growth of gastrointestinal stromal tumor xenograft

et al. 2011

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To investigate whether Endostar can inhibit the angiogenesis and growth of gastrointestinal stromal tumor (GIST) xenografts in nude mice and the feasibility of antiangiogenesis as a treatment modality for GIST. Twenty Balb/c-nu/nu mice burdened with GIST were randomly divided into two groups. Endostar (2 mg/kg) was injected around the tumor once per day for 10 days in the experimental group and with normal saline (NS) (0.1 ml) in the control group. The tumor bulk was measured every 5 days until 5 days after the end of the injections. The inhibition tumor rate (ITR) was calculated. Tumor bulk, microvascular density (MVD), rate of bcl-2-positive expression, and AI were assessed in the two groups. Tumor volumes were compared before and after treatment in the experimental group. The difference in tumor bulk between the two groups was not statistically significant before treatment (P = 0.628), but at the end of test, the difference was significant (P < 0.0001), and in the test group, the tumor bulk was also decreased significantly after treatment (P < 0.0001). The ITR was 86.5%. All xenografts showed CD117-positive staining. MVD and bcl-2-positive rate were lower in the experimental group than in the control group (P = 0.020 and P = 0.023, respectively). AI increased significantly in the experimental group compared with the control group (P = 0.020). Endostar can reduce angiogenesis,promote cell apoptosis, and inhibit the growth of a GIST xenograft. It is possible that Endostar will be used as an effective drug for GIST in the future.

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Prognostic significance of vascular endothelial growth factor expression in clear cell renal cell carcinoma

Cited by 30 publications

References 27 publications

Relationship Between Vascular Endothelial Growth Factor and Nuclear Factor-κB in Renal Cell Tumors

Relationship Between Vascular Endothelial Growth Factor and Nuclear Factor-κB in Renal Cell Tumors

MR classification of renal masses with pathologic correlation

The inhibition of Endostar on the angiogenesis and growth of gastrointestinal stromal tumor xenograft

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