Evaluation of venous thrombosis and tissue factor in epithelial ovarian cancer

Gynecol Oncol. 2017 Jul;146(1):146-152. doi: 10.1016/j.ygyno.2017.04.021. Epub 2017 May 10.

Abstract

Objective: Ovarian clear cell carcinoma (OCCC) and high grade serous ovarian cancer (HGSOC) are associated with the highest risk of VTE among patients with epithelial ovarian cancer (EOC). Tissue factor (TF) is a transmembrane glycoprotein which can trigger thrombosis. We sought to evaluate if there is an association between VTE and tumor expression of tissue factor (TF), plasma TF, and microvesicle TF (MV TF) activity in this high-risk population.

Methods: We performed a case-control study of OCCC and HGSOC patients with and without VTE. 105 patients who underwent surgery at a tertiary care center between January 1995 and October 2013 were included. Plasma TF was measured with an enzyme-linked immunosorbent assay. A TF-dependent Factor Xa generation assay was used to measure MV TF activity. Immunohistochemical (IHC) analysis was performed to evaluate tumor expression of TF.

Results: 35 women with OCCC or HGSOC diagnosed with VTE within 9months of surgery were included in the case group. Those with VTE had a worse OS, p<0.0001, with a greater than three-fold increase in risk of death, HR 3.33 (CI 1.75-6.35). There was no significant difference in median plasma TF level or MV TF activity level between patients with and without VTE. OCCC patients had greater expression of TF in their tumors than patients with HGSOC, p<0.0001.

Conclusions: TFMV activity and plasma TF level were not predictive of VTE in this patient population. Given the extensive expression of TF in OCCC tumors, it is unlikely IHC expression will be useful in risk stratification for VTE in this population.

Keywords: Clear cell carcinoma; Microvesicles; Ovarian cancer; Tissue factor; Venous thromboembolism.

Publication types

  • Evaluation Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Ovarian Epithelial
  • Case-Control Studies
  • Enzyme Multiplied Immunoassay Technique
  • Female
  • Humans
  • Immunohistochemistry
  • Middle Aged
  • Neoplasm Staging
  • Neoplasms, Glandular and Epithelial / blood*
  • Neoplasms, Glandular and Epithelial / pathology*
  • Ovarian Neoplasms / blood*
  • Ovarian Neoplasms / pathology*
  • Survival Analysis
  • Thromboplastin / biosynthesis
  • Thromboplastin / metabolism*
  • Venous Thrombosis / blood*
  • Venous Thrombosis / pathology*

Substances

  • Thromboplastin