Abstract
The von Hippel-Lindau (VHL) gene is often inactivated in sporadic renal cell carcinoma (RCC) by mutation or promoter hypermethylation. The prognostic or predictive value of VHL gene alteration is not well established. We conducted this meta-analysis to evaluate the association between the VHL alteration and clinical outcomes in patients with RCC. We searched PUBMED, MEDLINE and EMBASE for articles including following terms in their titles, abstracts, or keywords: ‘kidney or renal’, ‘carcinoma or cancer or neoplasm or malignancy’, ‘von Hippel-Lindau or VHL’, ‘alteration or mutation or methylation’, and ‘prognostic or predictive’. There were six studies fulfilling inclusion criteria and a total of 633 patients with clear cell RCC were included in the study: 244 patients who received anti-vascular endothelial growth factor (VEGF) therapy in the predictive value analysis and 419 in the prognostic value analysis. Out of 663 patients, 410 (61.8%) had VHL alteration. The meta-analysis showed no association between the VHL gene alteration and overall response rate (relative risk = 1.47 [95% CI, 0.81-2.67], P = 0.20) or progression free survival (hazard ratio = 1.02 [95% CI, 0.72-1.44], P = 0.91) in patients with RCC who received VEGF-targeted therapy. There was also no correlation between the VHL alteration and overall survival (HR = 0.80 [95% CI, 0.56-1.14], P = 0.21). In conclusion, this meta-analysis indicates that VHL gene alteration has no prognostic or predictive value in patients with clear cell RCC.
Highlights
Renal cell carcinoma (RCC) is the most common kidney cancer [1], and approximately 63,000 and 5,000 new cases of kidney cancer are diagnosed each year in the United States and Korea [2, 3]
von Hippel-Lindau (VHL) gene has an important role in regulation of the hypoxia pathway via the hypoxia inducible factors (HIFs) in sporadic RCC [7]
VHL gene has an important role in regulation of the hypoxia pathway via the HIFs in sporadic RCC [7]
Summary
Renal cell carcinoma (RCC) is the most common kidney cancer [1], and approximately 63,000 and 5,000 new cases of kidney cancer are diagnosed each year in the United States and Korea [2, 3]. The von Hippel-Lindau (VHL) gene is a tumor suppressor gene and VHL gene alteration occurs in 50-70% of clear cell RCC [5, 6]. VHL gene alteration plays a key role in RCC pathogenesis and provides plausible therapeutic target for anti-VEGF therapy, the clinical significance of VHL gene alteration in RCC has not been well established.
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