Human Cancer Biology Characterization of CD45 /CD31þ/CD105þ Circulating Cells in the Peripheral Blood of Patients with Gynecologic Malignancies

Purpose: Circulating endothelial cells (CEC) have been widely used as a prognostic biomarker and regarded as a promising strategy for monitoring the response to treatment in several cancers. However, the presence andbiologic roles of CECs have remained controversial for decades because technical standards for the identification and quantification of CECs have not been established. Here, we hypothesized that CECs detected by flow cytometry might be monocytes rather than endothelial cells. Experimental Design: The frequency of representative CEC subsets (i.e., CD45 /CD31þ, CD45 / CD31þ/CD146þ, CD45 /CD31þ/CD105þ) was analyzed in the peripheral blood of patients with gynecologic cancer (n 1⁄4 56) and healthy volunteers (n 1⁄4 44). CD45 /CD31þ cells, which are components of CECs, were isolated and the expression of various markers (CD146, CD105, vWF, and CD144 for endothelial cells; CD68 and CD14 for monocytes) was examined by immunocytochemistry. Results: CD45 /CD31þ/CD105þ cells were significantly increased in the peripheral blood of patients with cancer, whereas evaluation of CD45 /CD31þ/CD146þ cells was not possible both in patients with cancer and healthy controls due to the limited resolution of the flow cytometry. Immunocytochemistry analyses showed that these CD45 /CD31þ/CD105þ cells did not express vWF and CD146 but rather CD144. Furthermore, CD45 /CD31þ/CD105þ cells uniformly expressed the monocyte-specific markers CD14 and CD68. These results suggest that CD45 /CD31þ/CD105þ cells carry the characteristics of monocytes rather than endothelial cells. Conclusions: Our data indicate that CD45 /CD31þ/CD105þ circulating cells, which are significantly increased in the peripheral bloodof patientswith gynecologic cancer, aremonocytes rather than endothelial cells. Further investigation is required to determine the biologic significance of their presence and function in relation with angiogenesis. Clin Cancer Res; 1–11. 2013 AACR.