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The Use of Reverse Phase Protein Arrays RPPA to Explore Protein Expression Variation within Individual Renal Cell Cancers
Published on: January 22, 2013
Analyses of Potential Predictive Markers and Response to Targeted Therapy in Patients with Advanced Clear-cell Renal
Yan Song, Jing Huang1, Ling Shan
1Department of Medical Oncology, Cancer Hospital (Institute), Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100021, China.
Background:
Vascular endothelial growth factor-targeted agents are standard treatments in advanced clear-cell renal cell carcinoma (ccRCC), but biomarkers of activity are lacking. The aim of this study was to investigate the association of Von Hippel-Lindau (VHL) gene status, vascular endothelial growth factor receptor (VEGFR) or stem cell factor receptor (KIT) expression, and their relationships with characteristics and clinical outcome of advanced ccRCC.
Methods:
A total of 59 patients who received targeted treatment with sunitinib or pazopanib were evaluated for determination at Cancer Hospital and Institute, Chinese Academy of Medical Sciences between January 2010 and November 2012. Paraffin-embedded tumor samples were collected and status of the VHL gene and expression of VEGFR and KIT were determined by VHL sequence analysis and immunohistochemistry. Clinical-pathological features were collected and efficacy such as response rate and Median progression-free survival (PFS) and overall survival (OS) were calculated and then compared based on expression status. The Chi-square test, the Kaplan-Meier method, and the Lon-rank test were used for statistical analyses.
Results:
Of 59 patients, objective responses were observed in 28 patients (47.5%). The median PFS was 13.8 months and median OS was 39.9 months. There was an improved PFS in patients with the following clinical features: Male gender, number of metastatic sites 2 or less, VEGFR-2 positive or KIT positive. Eleven patients (18.6%) had evidence of VHL mutation, with an objective response rate of 45.5%, which showed no difference with patients with no VHL mutation (47.9%). VHL mutation status did not correlate with either overall response rate (P = 0.938) or PFS (P = 0.277). The PFS was 17.6 months and 22.2 months in VEGFR-2 positive patients and KIT positive patients, respectively, which was significantly longer than that of VEGFR-2 or KIT negative patients (P = 0.026 and P = 0.043).
Conclusion:
VHL mutation status could not predict the efficacy of sunitinib or pazopanib. Further investigation of VHL/VEGFR pathway components is needed.
Insights
Biomarkers for advanced clear-cell renal cell carcinoma (ccRCC) targeted therapies are needed. VEGFR-2 or KIT expression, not VHL gene status, predicted progression-free survival in patients receiving sunitinib or pazopanib.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Vascular endothelial growth factor-targeted agents are standard treatments for advanced clear-cell renal cell carcinoma (ccRCC).
- Biomarkers to predict treatment efficacy are currently lacking.
- This study investigated potential biomarkers including Von Hippel-Lindau (VHL) gene status and receptor expression.
Purpose of the Study:
- To investigate the association of VHL gene status, vascular endothelial growth factor receptor (VEGFR), and stem cell factor receptor (KIT) expression.
- To determine the relationship of these factors with clinical characteristics and outcomes in advanced ccRCC.
- To identify predictive biomarkers for targeted therapies in ccRCC.
Main Methods:
- Retrospective analysis of 59 patients with advanced ccRCC treated with sunitinib or pazopanib.
- VHL gene sequencing and immunohistochemistry for VEGFR and KIT expression.
- Statistical analysis including Chi-square test, Kaplan-Meier method, and log-rank test to compare outcomes.
Main Results:
- Objective response rate was 47.5%, median progression-free survival (PFS) was 13.8 months, and median overall survival (OS) was 39.9 months.
- VHL mutation status did not correlate with response rate or PFS.
- PFS was significantly longer in patients with positive VEGFR-2 (17.6 months) or KIT (22.2 months) expression compared to negative expression.
Conclusions:
- VHL mutation status is not a reliable predictor of sunitinib or pazopanib efficacy in advanced ccRCC.
- VEGFR-2 and KIT expression levels are associated with improved PFS.
- Further research into the VHL/VEGFR pathway is warranted to identify better biomarkers.
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