Microvessel area as a predictor of sorafenib response in metastatic renal cell carcinoma
Saadia A Aziz1, Joshua A Sznol1, Laurence Albiges2
1Departments of Medicine, Section of Medical Oncology, Yale University School of Medicine, 333 Cedar St., WWW213, New Haven, CT 06520, USA.
Background:
Sorafenib was the first Food and Drug Administration approved anti-angiogenic therapy for renal cell carcinoma (RCC). Currently, there are no validated predictive biomarkers for sorafenib. Our purpose was to determine if sorafenib target expression is predictive of sorafenib sensitivity.
Methods:
We used an automated, quantitative immunofluorescence-based method to determine expression levels of sorafenib targets VEGF, VEGF-R1, VEGF-R2, VEGF-R3, c-RAF, B-RAF, c-Kit, and PDGFR-β in a cohort of 96 patients treated with sorafenib. To measure vasculature in the tumor samples, we measured microvessel area (MVA) by CD-34 staining.
Results:
Of the markers studied, only high MVA was predictive of response (p = 0.005). High MVA was associated with smaller primary tumors (p = 0.005). None of the biomarkers studied was predictive of overall or progression-free survival. Using the Bonferroni adjustment correcting for 9 variables with an alpha of 0.05, MVA remained significantly associated with sorafenib response.
Conclusions:
Our results suggest that high MVA in tumor specimens might be associated with a greater likelihood of response to therapy. Further studies are needed to confirm these results in additional patients and in patients receiving other VEGF-R2 inhibitors, as MVA might be useful to improve patient selection for VEGF-R2 inhibitors.
Insights
High microvessel area (MVA) in renal cell carcinoma (RCC) tumors predicts response to sorafenib therapy. This finding may help select patients for anti-angiogenic treatments targeting VEGF-R2.
Area of Science:
- Oncology
- Translational Research
- Biomarker Discovery
Background:
- Sorafenib is an FDA-approved anti-angiogenic therapy for renal cell carcinoma (RCC).
- Currently, no validated predictive biomarkers exist for sorafenib treatment efficacy.
- This study investigated sorafenib target expression as a predictor of treatment sensitivity.
Purpose of the Study:
- To determine if sorafenib target expression predicts sorafenib sensitivity in RCC patients.
- To identify potential biomarkers for predicting response to sorafenib therapy.
Main Methods:
- Utilized automated, quantitative immunofluorescence to measure expression of sorafenib targets (VEGF, VEGF-R1, VEGF-R2, VEGF-R3, c-RAF, B-RAF, c-Kit, PDGFR-β) in 96 RCC patients.
- Assessed tumor vasculature by measuring microvessel area (MVA) using CD-34 staining.
Main Results:
- High microvessel area (MVA) was the only significant predictor of sorafenib response (p=0.005).
- High MVA correlated with smaller primary tumor size (p=0.005).
- No studied biomarkers predicted overall or progression-free survival.
Conclusions:
- High MVA in tumor specimens may indicate a higher likelihood of response to sorafenib.
- MVA could potentially improve patient selection for anti-angiogenic therapies, particularly VEGF-R2 inhibitors.
- Further validation in larger patient cohorts and with other VEGF-R2 inhibitors is warranted.
