Levels of circulating CD45 dim CD34 VEGFR2 progenitor cells correlate with outcome in metastatic renal cell carcinoma patients treated with tyrosine kinase inhibitors

F. Farace, M. Gross-Goupil, E. Tournay, M. Taylor, N. Vimond, N. Jacques, F. Billiot, A. Mauguen, C. Hill, B. Escudier

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    Abstract

    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 1 ml 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-1α 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-1α, sVCAM-1 levels with PFS and OS was observed. However, baseline CD45 dim CD34 VEGFR2 7AAD progenitor cell levels were associated with PFS (P0.01) and OS (P0.006). Changes in this population and in SDF-1α levels between day 1 and day 14 were associated with PFS (P0.03, P0.002). Changes in VEGF and SDF-1α levels were associated with OS (P0.02, P0.007).Conclusion:Monitoring CD45 dim CD34 VEGFR2 progenitor cells, plasma VEGF and SDF-1α levels could be of clinical interest in TKI-treated mRCC pts to predict outcome.

    Original languageEnglish
    Pages (from-to)1144-1150
    Number of pages7
    JournalBritish Journal of Cancer
    Volume104
    Issue number7
    DOIs
    Publication statusPublished - 29 Mar 2011

    Keywords

    • angiogenesis
    • biomarker
    • circulating endothelial cells
    • circulating endothelial progenitor cells
    • metastatic renal cell carcinoma
    • tyrosine kinase inhibitors

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