Microvessel area as a predictor of sorafenib response in metastatic renal cell carcinoma

Cancer Cell International

Harriet M Kluger²  Bernard Escudier¹  Robert L Camp³  Lucia B Jilaveanu²  Christopher Zito²  Laurence Albiges¹  Joshua A Sznol²  Saadia A Aziz² 

[1] Department of Medical Oncology, Institut Gustave Roussy, Villejuif, France;Departments of Medicine, Section of Medical Oncology, Yale University School of Medicine, 333 Cedar St., WWW213, New Haven, CT 06520, USA;Departments of Medicine and Pathology, Yale University School of Medicine, New Haven, CT, USA

关键词: Sorafenib;    Angiogenesis;    Microvessel area;    Renal cell carcinoma;   

Others  :  792455
DOI  :  10.1186/1475-2867-14-4

 received in 2013-10-14, accepted in 2014-01-10,  发布年份 2014

【 摘 要 】

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.

【 授权许可】

   
2014 Aziz et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

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