Prognostic value of circulating endothelial cells in metastatic colorectal cancer

Abstract

BACKGROUNDThere is urgent need for improved staging in patients with metastatic colorectal cancer (mCRC). In this study, we evaluated the prognostic value of circulating endothelial cells (CEC) in comparison with circulating tumor cells (CTC) in patients with mCRC amenable for potentially curative surgery.METHODSA total of 140 patients were enrolled prospectively. CTC and CEC were measured with the CellSearch System (Veridex, NJ, USA). Cut-off values were determined using ROC analyses. Prognostic factors were identified by Cox proportional hazards models.RESULTSROC analyses revealed ≥ 21 CEC as cut-off levels for detection, which was present in 68 (49%). CEC detection was associated with female gender (p = 0.03) only, whereas CTC detection was associated with presence of the primary tumor (p = 0.007), metastasis size (p < 0.001), bilobar liver metastases (p = 0.02), CEA (p < 0.001) and CA 19-9 levels (p < 0.001). On multivariate analysis only CEC detection (HR 1.81; p = 0.03) and preoperative CA19-9 levels (HR 2.28, p = 0.005) were revealed as independent predictors of poor survival.CONCLUSIONSCEC are of stronger prognostic value than CTC. Further studies are required to validate these results and to evaluate CEC as predictive biomarker for systemic therapy alone as well as in combination with other markers such as CA19-9.

CD276-Positive Circulating Endothelial Cells Do Not Predict Response to Systemic Therapy in Advanced Colorectal Cancer

“…Studies from CEC counts prior to liver resections reported 5/mL (CellSearch, 140 patients) or 10 vs. 20/mL for patients with respectively good (n = 102) or poor (n = 52) outcome, (CD34 + CD45 − CD146 + measured by FACS). [20,21]. In this study, a significant higher CEC count after three cycles of chemotherapy (p = 0.00), with a nearly 2-fold increase (48 to 90/4 mL) was detected.…”

“…Both studies used the CellSearch system (by Veridex ® , Menarini Silicon Biosystems Inc. Huntington Valley, PA 19006, USA), one showing no prognostic value for PFS or OS [18], the other increase of PFS and OS for baseline CEC counts < 65/mL [19]. In a third prospective series, CEC ≤ 21/4 mL was found to be an independent prognostic factor of poor survival for patients with mCRC amenable for potentially curative surgery, which was of stronger prognostic value than circulating tumor cells [20]. The flow cytometry enumeration we used, as described before by Kraan et al has the same markers for CEC identification, albeit with different fluorescent antibodies.…”

The Blood Circulating Rare Cell Population. What Is It and What Is It Good for?

“…This notion was supported by Ilie et al [78] who investigated the usefulness of CD164+ circulating EnC counting in combination with CD164 serum level detection for predicting clinical outcomes in non-small cell lung carcinoma patients undergoing surgery, showing that marker elevation in both cases at baseline correlated positively with poor prognosis. Similar investigations with respect to the detection platform and outcome have been conducted for breast and colorectal cancer [60,83]. Moreover, Rahbari et al [83] compared circulating EnC with epithelial CTC for prognostic performance in metastatic colorectal cancer using the CellSearch system.…”

“…Similar investigations with respect to the detection platform and outcome have been conducted for breast and colorectal cancer [60,83]. Moreover, Rahbari et al [83] compared circulating EnC with epithelial CTC for prognostic performance in metastatic colorectal cancer using the CellSearch system. The authors reported a higher hazard ratio associated with overall survival (OS) in case of circulating EnC when compared to CTC.…”

“…The authors reported a higher hazard ratio associated with overall survival (OS) in case of circulating EnC when compared to CTC. Nevertheless, the overall benefit of circulating CTC and EnC in this liquid biopsy application stands in question as the hazard ratio values are low and outperformed by the serum marker CA 19-9 [83]. Of note is one report that seems to disagree with the general notion of worse prognosis upon circulating EnC elevation at baseline using the same technology when referred to Ali et al [60,84].…”