Potential use of circulating endothelial cells as a biomarker of renal cell carcinoma.

Each year, renal cell carcinoma (RCC) accounts for significant mortality in the population. Whilst the disease is now being diagnosed earlier, determining patient prognosis remains a challenge. Current prognostic indicators, such as TNM stage, Fuhrman grade, and RCC subtype, are inadequate. Unlike several other malignancies, RCC lacks a biomarker that can stratify patients into high, intermediate, or low risk for developing metastases. Additionally, antiangiogenic therapy is currently offered to patients with metastatic disease, however, a biomarker to monitor treatment efficacy is lacking. Recent attention has focused on surrogate markers of tumor vascularization as a source of prognostic biomarkers, as tumor growth is ultimately dependent on neovascularization. Two cell populations of interest, circulating endothelial cells (CECs) and circulating endothelial progenitors (CEPs), have been demonstrated across several studies to contribute to tumor vascularization. Given these findings, studies have examined their utility as biomarkers of prognosis by correlating their levels with progression-free survival and prognostic determinants such as tumor volume and weight. However, their role in predicting prognosis in RCC, as well as their potential to act as markers of treatment efficacy in metastatic RCC, remains to be established. Previous studies on CECs and CEPs in the context of cancer will be outlined in this review.

Circulating endothelial cells and progenitors: potential biomarkers of renal cell carcinoma.

OBJECTIVE: To compare the levels of circulating endothelial cells (CECs) and progenitors (CEPs) between tumour-bearing mice and healthy controls, in human renal cell carcinoma (RCC) xenograft models. The secondary objective was to correlate CEC and CEP levels with tumour variables such as tumour volume, weight and vascularity, indicators of disease severity. MATERIALS AND METHODS: Two human RCC xenograft models were used. Tumour cells were inoculated either subcutaneously or beneath the renal subcapsule (orthotopic). Tumour dimensions were recorded and blood samples were taken throughout the experiment, as well as at the end of the experiment, upon which tumours were excised and prepared for histological examination. All blood samples were analysed by flow cytometry. RESULTS: CEC and CEP levels were significantly elevated in tumour-bearing mice compared with healthy controls. In particular, there was a divergence in CEC levels between RCC-bearing mice and controls during early phases in disease, whereas CEP levels were only elevated towards the end. Additionally, CEC levels correlated with tumour variables such as tumour volume, when tumour volume was <200 mm³ and with tumour vascularity in certain models. CEP levels did not correlate significantly with most tumour variables examined. CONCLUSION: In human RCC xenograft models, CEC levels showed promise as an adjuvant biomarker in evaluating disease burden. RESULTS from correlating CEC levels with tumour variables such as tumour volume, weight and vascularity suggested that CEC levels were a better prognostic indicator during early phases of tumour growth. CEP levels were elevated in tumour-bearing mice compared with controls; however, enumerated numbers were small and require further validation in future studies.