Levels of circulating CD45dimCD34+VEGFR2+ progenitor cells correlate with outcome in metastatic renal cell carcinoma patients treated with tyrosine kinase inhibitors

BACKGROUND: Predicting the efficacy of antiangiogenic therapy would be of clinical value in patients (pts) with metastatic renal cell carcinoma (mRCC). We tested the hypothesis that circulating endothelial cell (CEC), bone marrow-derived CD45(dim)CD34(+) VEGFR2(+) progenitor cell or plasma angiogenic factor levels are associated with clinical outcome in mRCC pts undergoing treatment with tyrosine kinase inhibitors (TKI). METHODS: Fifty-five mRCC pts were prospectively monitored at baseline (day 1) and day 14 during treatment (46 pts received sunitinib and 9 pts received sorafenib). Circulating endothelial cells (CD45(-)CD31(+)CD146(+)7-amino-actinomycin (7AAD)(-) cells) were measured in 1ml whole blood using four-color flow cytometry (FCM). Circulating CD45(dim)CD34(+)VEGFR2(+)7AAD(-) progenitor cells were measured in progenitor-enriched fractions by four-color FCM. Plasma VEGF, sVEGFR2, SDF-1 alpha and sVCAM-1 levels were determined by ELISA. Correlations between baseline CEC, CD45(dim)CD34(+)VEGFR2(+)7AAD(-) progenitor cells, plasma factors, as well as day 1-day 14 changes in CEC, CD45(dim)CD34(+)VEGFR2(+)7AAD(-) progenitor, plasma factor levels, and response to TKI, progression-free survival (PFS) and overall survival (OS) were examined. RESULTS: No significant correlation between markers and response to TKI was observed. No association between baseline CEC, plasma VEGF, sVEGFR-2, SDF-1 alpha, sVCAM-1 levels with PFS and OS was observed. However, baseline CD45(dim)CD34(+) VEGFR2(+)7AAD(-) progenitor cell levels were associated with PFS (P = 0.01) and OS (P = 0.006). Changes in this population and in SDF-1 alpha levels between day 1 and day 14 were associated with PFS (P = 0.03, P = 0.002). Changes in VEGF and SDF-1 alpha levels were associated with OS (P = 0.02, P = 0.007). CONCLUSION: Monitoring CD45(dim)CD34(+)VEGFR2(+) progenitor cells, plasma VEGF and SDF-1 alpha levels could be of clinical interest in TKI-treated mRCC pts to predict outcome. British Journal of Cancer (2011) 104, 1144-1150. doi: 10.1038/bjc.2011.72 www.bjcancer.com Published online 8 March 2011 (c) 2011 Cancer Research UK