Levels of a subpopulation of platelets, but not circulating endothelial cells, predict early treatment failure in prostate cancer patients after prostatectomy

Abstract

Background: Angiogenesis is one of the hallmarks of cancer driving tumour growth and ultimately metastasis. Circulating endothelial cells (CECs) and circulating endothelial progenitor (CEPs) cells have been reported as candidate surrogate markers for tumour vascularisation. Our aim was to investigate the potential use of these circulating cells levels as predictors of prostate cancer treatment failure and metastasis. Methods: We examined the levels of CD31 + CD45- cells (CECs) and CD31+ CD45- CD117 (CEPs) in s.c. and orthotopic models of human prostate cancers and correlated measurements with tumour size, volume and microvessel density (MVD). We then performed a prospective cohort study in 164 men with localised prostate cancer undergoing prostatectomy. The CD31+ CD45- , CD31+ CD45- CD146 (CECs) and CD31+ CD45 - intermediate CD133 (CEPs) populations were quantified and subsequently enriched for further characterisation. Results: In preclinical models, levels of CD31+ CD45- cells, but not CEPs, were significantly elevated in tumour-bearing mice and correlated with tumour size, volume and MVD. In our human prospective cohort study, the levels of CD31 + CD45- cells were significantly higher in men who experienced treatment failure within the first year, and on logistic regression analysis were an independent predictor of treatment failure, whereas neither levels of CECs or CEPs had any prognostic utility. Characterisation of the isolated CD31+ CD45- cell population revealed an essentially homogenous population of large, immature platelets representing 0.1% of circulating platelets. Conclusion: Elevated levels of a distinct subpopulation of circulating platelets were an independent predictor for early biochemical recurrence in prostate cancer patients within the first year from prostatectomy. © 2012 Cancer Research UK All rights reserved.