Correlation of endothelial angiopoietin-2 expression with tumor angiogenesis and response to sunitinib in metastatic renal cell carcinoma.

Abstract

461 Background: The endothelial growth factor angiopoietin-2 (Ang2) is a target for novel anti-angiogenic therapies, but its potential as a biomarker remains unknown. Methods: We evaluated Ang2, CD31 and Ki67 expression in tumors of 136 patients with metastatic RCC (mRCC) treated with first-line sunitinib from tumor samples. Results: Ang2 was exclusively expressed in the endothelial cells of tumor blood vessels. Using a cutoff of ≥50 Ang2+ vessels/microscopic field, 38% of the samples had high Ang2 expression. High Ang2 expression correlated with high CD31+ vessel density (p=0.002). 91% of patients with high Ang2 expression had partial response (PR) or stable disease (SD) as best response to sunitinib compared to 76% of those with low Ang2 expression (p=0.033). High CD31+ vessel density correlated with high clinical benefit rate (p=0.015), and with low levels of Ki-67+ tumor cells (p=0.018). Combined high expression of both Ang2 and CD31 predicted a better clinical benefit rate with 100% of the patients with high Ang2 and CD31 expression (n=25) achieving PR/SD compared to 77% among the rest of the patients (n=101; p=0.007). Only one (8%, n=12) patient with papillary RCC had high Ang2 expression, whereas 49 (41%, n = 120) patients with clear cell RCC had high Ang2 expression (p=0.03). Conclusions: In this first study to investigate Ang2 expression and outcome in mRCC patients treated with an angiogenesis inhibitor, high Ang2 expression in the tumor vasculature was predictive for sunitinib efficacy.