Current management and future directions in the treatment of advanced renal cell carcinoma-a latin american perspective: 10 years in review

Smaletz, Òren

doi:10.1590/s1677-5538.ibju.2014.0651

Cited by 11 publications

(9 citation statements)

References 40 publications

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“…From an improved understanding of the molecular biology of RCCs during the last decade, new molecular targeted agents have emerged for patients with advanced RCC [ 5 , 6 , 7 , 8 , 17 ]. VHL gene encodes a multifunctional protein (pVHL) which has an important role in regulation of the hypoxia pathway via the HIFs in sporadic RCCs [ 11 ].…”

Section: Discussionmentioning

confidence: 99%

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Clinicopathologic Significance of VHL Gene Alteration in Clear-Cell Renal Cell Carcinoma: An Updated Meta-Analysis and Review

Kim

Jang

et al. 2018

IJMS

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The von Hippel-Lindau (VHL) gene is inactivated frequently in sporadic clear-cell renal cell carcinomas (ccRCCs) by genetic alteration (mutation, loss of heterozygosity, or promoter hypermethylation). However, the pathological or prognostic significance of VHL gene alteration has not been well defined. We conducted this meta-analysis to evaluate the association between VHL alteration and clinopathologic findings in ccRCCs. We performed a systematic computerized search of online databases, including PubMed, EMBASE, Web of Science, and Google Scholar (up to July 2018). From ten studies, 1,082 patients were included in the pooled analyses of odds ratios (ORs) with 95% confidence intervals (CIs) for pathological features (nuclear grade and disease stage) or hazard ratios (HRs) with 95% CIs for overall survival (OS). VHL alteration was not significantly associated with nuclear grade (OR = 0.79, 95% CI: 0.59–1.06, p = 0.12) or disease stage (OR = 1.07, 95% CI: 0.79–1.46, p = 0.65). There was also no significant correlation between VHL alteration and OS (HR = 0.75, 95% CI: 0.43–1.29, p = 0.30). When we pooled HRs for OS according to the VHL alteration types, the combined HRs were 0.72 (95% CI: 0.47–1.11, p = 0.14) for VHL mutations and 1.32 (95% CI: 0.70–2.47, p = 0.39) for methylation. In conclusion, this meta-analysis indicates that VHL gene alteration is not significantly associated with the pathological features and survival in patients with ccRCC.

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Section: Discussionmentioning

confidence: 99%

“…However, about 30% of patients who received curative resection experience disease recurrence [ 4 ]. Despite the recent introduction of new molecular targeted agents, the prognosis of recurrent or metastatic RCC is very poor, with 5-year survival rate of about 10% [ 5 , 6 , 7 , 8 ].…”

Section: Introductionmentioning

confidence: 99%

Clinicopathologic Significance of VHL Gene Alteration in Clear-Cell Renal Cell Carcinoma: An Updated Meta-Analysis and Review

Kim

Jang

et al. 2018

IJMS

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“…Most patients with RCC are symptom-free in the early stage, and more than 50% of RCCs are found coincidentally by physical examination and imaging [ 3 ]. Approximately 30% of the patients with RCC have developed metastases, and the average 5-year survival rate is just 12.3% [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

Clinical significance of p16INK4A and p14ARF promoter methylation in renal cell carcinoma: a meta-analysis

Ren¹,

Weng³

et al. 2017

Oncotarget

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The inactivation of p16INK4A and p14ARF via promoter methylation has been investigated in various cancers. However, the clinical effects of p16INK4A and p14ARF promoter methylation on renal cell carcinoma (RCC) remain to be clarified. The pooled data were calculated and summarized. Finally, an investigation of 14 eligible studies with 1231 RCC patients and 689 control patients was performed. Methylated p16INK4A and p14ARF were observed to be significantly higher in RCC than in control subjects without malignancies (OR = 2.77, P = 0.005; OR = 11.73, P < 0.001, respectively). Methylated p16INK4A was significantly associated with the risk of RCC in the tissue subgroup, but not in the serum and urine subgroups. Methylated p16INK4A was significantly associated with tumor size. We did not find that p16INK4A promoter methylation was associated with sex, tumor grade, lymph node status, and tumor histology. Methylated p14ARF was significantly correlated with sex and tumor histology. Three studies reported that p16INK4A methylation was not significantly correlated with the prognosis of RCC. The results suggested that p16INK4A and p14ARF promoter methylation may be correlated with the carcinogenesis of RCC, and that methylated p14ARF, especially, can be a major susceptibility gene. We also found the different clinicopathological significance of 16INK4A and p14ARF in RCC. Additional studies with sufficient data are essential to further evaluate the clinical features and prognostic effect of p16INK4A and p14ARF promoter methylation in RCC.

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“…Generally, RCC is asymptomatic in its early stages, and more than 50% of RCCs are detected incidentally by examinations, such as ultrasound and computed tomography (CT). Approximately 25%-30% of the patients with RCC are defined as cases with advanced or metastatic RCC, and the 5-year survival rate is only 12.3% [3].…”

Section: Introductionmentioning

confidence: 99%

The Clinicopathological Significance of Epigenetic Silencing of VHL Promoter and Renal Cell Carcinoma: A Meta-Analysis

Yang

Zhao²,

Zhao³

et al. 2016

Cell Physiol Biochem

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Background/Aims: Von Hippel-Lindau gene (VHL) has been reported as a tumor-suppressor gene in some cancers. However, the association between VHL promoter hypermethylation and renal cell carcinoma (RCC) remains to be clarified. We are the first to systematically integrate published papers to assess the role of hypermethylated VHL in RCC. Methods: The potential relevant papers were searched via PubMed, Embase, EBSCO, CNKI, and Wanfang databases. The overall odds ratio (OR) and corresponding 95% confidence interval (95% CI) were calculated to evaluate the relationship between VHL promoter hypermethylation and RCC. Results: Finally, a total of 1,998 RCC patients and 294 controls from 13 eligible articles were included in this meta-analysis. Under the fixed-effects model, the pooled OR from seven studies including 596 RCC and 294 nonmalignant samples showed that VHL promoter hypermethylation was significantly higher in cancer than in controls (OR = 7.93, 95% CI = 2.84- 22.15, P < 0.001). Subgroup analysis based on ethnic population and testing method revealed that hypermethylated VHL had a significantly similar OR value in different races and detection methodologies. No significant association was found between hypermethylated VHL and tumor grade, tumor stage, tumor size, histological types, and lymph node status in cancer (all P > 0.05). In the current study, there was no evidence of publication bias as determined by Egger's test (all P > 0.05). Conclusions: In the investigated patients, VHL promoter hypermethylation, which may play an important role in carcinogenesis of RCC, is significantly associated with an increased risk of RCC. However, VHL promoter hypermethylation is not correlated with specific clinicopathological characteristics. Additional future studies are needed to confirm our results.

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Current management and future directions in the treatment of advanced renal cell carcinoma-a latin american perspective: 10 years in review

Cited by 11 publications

References 40 publications

Clinicopathologic Significance of VHL Gene Alteration in Clear-Cell Renal Cell Carcinoma: An Updated Meta-Analysis and Review

Clinicopathologic Significance of VHL Gene Alteration in Clear-Cell Renal Cell Carcinoma: An Updated Meta-Analysis and Review

Clinical significance of p16INK4A and p14ARF promoter methylation in renal cell carcinoma: a meta-analysis

The Clinicopathological Significance of Epigenetic Silencing of VHL Promoter and Renal Cell Carcinoma: A Meta-Analysis

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