Abstract
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.
Highlights
Renal cell carcinoma (RCC) is the second common malignancy after bladder cancer in the urinary system, accounting for approximately 63,000 and 5000 new cases diagnosed each year in the United States and South Korea, respectively [1,2]
von Hippel-Lindau (VHL) gene alteration accounts for the vast majority of sporadic clear-cell renal cell carcinomas (ccRCCs) and provides plausible therapeutic target for anti-angiogenic agents, its clinicopathologic significance is still controversial with conflicting results among studies
In the current meta-analysis, we evaluated the pathological and prognostic value of VHL alteration in patients only with ccRCC
Summary
Renal cell carcinoma (RCC) is the second common malignancy after bladder cancer in the urinary system, accounting for approximately 63,000 and 5000 new cases diagnosed each year in the United States and South Korea, respectively [1,2]. RCCs comprise a group of heterogeneous tumors with distinct molecular alterations. Complete surgical resection is considered to be a curative treatment option for RCCs at the early or locally advanced stage. 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]
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