Clinical significance of circulating tumor cells in predicting disease progression and chemotherapy resistance in patients with gestational choriocarcinoma

Int J Cancer. 2019 Mar 15;144(6):1421-1431. doi: 10.1002/ijc.31742. Epub 2018 Oct 26.

Abstract

Gestational choriocarcinoma (GC) is a highly aggressive tumor. In our study, we systematically investigated EpCAM/CD147 expression characteristics in patients with GC and assessed the role of circulating tumor cells (CTCs) in predicting chemotherapy response and disease progression. GC tissues were positive for either epithelial cellular adhesion molecule (EpCAM) or CD147, and all samples exhibited strong human chorionic gonadotropin (HCG) expression. Among all the recruited patients (n = 115), 103 had at least 1 CTC in a 7.5-mL peripheral blood sample, and the percentage of patients with ≥4 CTCs in a particular FIGO stage group increased with a higher FIGO stage (p < 0.001). Furthermore, the pretreatment CTC count was related to tumor size (r = 0.225, p = 0.015) and the number of metastases (r = 0.603, p < 0.001). A progression analysis showed that among the 115 included patients who qualified for further examination, 52 of the 64 patients defined as progressive had ≥4 pretreatment CTCs, while only 7 of the 51 non-progressive patients had ≥4 pretreatment CTCs (p < 0.001). In multivariate analysis, CTCs (≥4) remained the strongest predictor of PFS when other prognostic markers, FIGO score and FIGO stage were included. Moreover, based on the chemotherapy response, patients with ≥4 CTCs were more likely to be resistant to chemotherapy than those with <4 CTCs (P < 0.001). These findings demonstrates the feasibility of CTC detection in cases of GC by adopting EpCAM/CD147 antibodies together as capturing antibodies. The CTC count is a promising indicator in the evaluation of biological activities and the chemotherapy response in GC patients.

Keywords: chemotherapy resistance; circulating tumor cell; gestational choriocarcinoma; progression; β-HCG.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Basigin / metabolism
  • Biomarkers, Tumor / metabolism*
  • Biopsy
  • Cell Count
  • Cell Line, Tumor
  • Choriocarcinoma / blood*
  • Choriocarcinoma / drug therapy
  • Choriocarcinoma / mortality
  • Choriocarcinoma / pathology
  • Chorionic Gonadotropin / metabolism
  • Disease Progression
  • Drug Resistance, Neoplasm*
  • Epithelial Cell Adhesion Molecule / metabolism
  • Feasibility Studies
  • Female
  • Follow-Up Studies
  • Humans
  • Middle Aged
  • Neoplasm Staging
  • Neoplastic Cells, Circulating*
  • Progression-Free Survival
  • Risk Factors
  • Young Adult

Substances

  • Antineoplastic Agents
  • BSG protein, human
  • Biomarkers, Tumor
  • Chorionic Gonadotropin
  • EPCAM protein, human
  • Epithelial Cell Adhesion Molecule
  • Basigin