Characterization of CD45^-/CD31⁺/CD105⁺ 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 and biologic 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 CD31⁺, CD45/CD31 ⁺/CD146⁺, CD45^-/CD31⁺/CD105 ⁺) was analyzed in the peripheral blood of patients with gynaecologic cancer (n = 56) and healthy volunteers (n = 44). CD45^-/CD31 ⁺ 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^-/CD31⁺/CD105⁺ cells were significantly increased in the peripheral blood of patients with cancer, whereas evaluation of CD45^-/CD31⁺/CD146⁺ 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^-/CD31⁺/CD105⁺ cells did not express vWF and CD146 but rather CD144. Furthermore, CD45^-/CD31 ⁺/CD105⁺cells uniformly expressed the monocyte-specific markers CD14 and CD68. These results suggest that CD45^-/CD31 ⁺/CD105⁺ cells carry the characteristics of monocytes rather than endothelial cells. Conclusions: Our data indicate that CD45 ^-/CD31⁺/CD105⁺ circulating cells, which are significantly increased in the peripheral blood of patients with gynecologic cancer, are monocytes rather than endothelial cells. Further investigation is required to determine the biologic significance of their presence and function in relation with angiogenesis.