Current and future role of circulating tumor cells in patients with epithelial ovarian cancer

Abstract

Circulating tumor cells (CTCs) are viable tumor cells that are released into the circulatory system. CTCs have shown a prognostic value in numerous solid tumors. CTC research in epithelial ovarian carcinoma (EOC) has attracted only little attention. Since the primary route of metastasis in EOC is considered to be direct peritoneal spread in the abdominal cavity and distant metastases only occur in one third of the patients, it was thought that there is not enough shedding of tumor cells in the circulation. Nevertheless recent studies revealed an important role of hematogenous spread in EOC and showed that CTC status is associated with advanced tumor stage, CA-125 levels and residual disease after surgery. Furthermore the presence of CTCs correlates with shorter overall and disease free survival. However this prognostic value of CTCs in EOC seems to depend on the used isolation and detection methods. In EOC function- or density based enrichment methods seem to offer more promising results then epithelial cell adhesion molecule (EpCAM)-based approaches. This can be explained by a low number of EpCAM positive CTCs in EOC and the downregulation of EpCAM during epithelial-to-mesenchymal transition (EMT). The presence of CTCs might also have predictive value as CTC status was associated with treatment response in two studies and CTCs showed to be a better monitoring tool then CA-125 in a small population. The (genotypic) characterization of CTCs might become even more important in the future paving the way for CTCs to a true predictive "liquid tumor biopsy".

Liquid biopsy in ovarian cancer: recent advances on circulating tumor cells and circulating tumor DNA

“…Different detection methods were used, mainly based on immunocytochemistry (microscopic detection or the FDA-approved CellSearch ® system), RT-PCR (AdnaTest, QIAGEN, Hilden, Germany), and RT-qPCR for the quantification of CTCs levels [20,21]. The time point of blood collection also differed, however, in the majority of studies the peripheral blood samples were obtained before surgical removal of the tumor.…”

Circulating Tumor Cells Enumerated by a Centrifugal Microfluidic Device as a Predictive Marker for Monitoring Ovarian Cancer Treatment: A Pilot Study

“…Moreover, CTC analysis enables the detection of multiple mutations within a single cell, which contributes to an improved understanding of tumor heterogeneity and clonal evolution to establish a potential connection between mutational status and pathway activation by combining CTC genomics and transcriptomics [37]. However, the limitations include the lack of large-scale studies with standardized approaches to enrich and detect CTCs [38]. Most of the studies on ovarian CTCs using the FDA-approved CellSearch system reported negative results due to its comparatively low accuracy in CTC detection and the limited availability of patients with ovarian cancer.…”

Circulating tumor cells enumerated by a centrifugal microfluidic device as a predictive marker for treatment monitoring of ovarian cancer patients

“…Moreover, CTC analysis enables the detection of multiple mutations within a single cell which contributes to the understanding of tumor heterogeneity and clonal evolution, and this might establish a potential connection between mutational status and pathway activation by combining the genomics and transcriptomics of CTCs [23]. However, some limitations have to be overcome such as the lack of large scale studies with standardized approaches to enrich and detect CTCs [24].…”