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Expression of Tissue Factor in Epithelial Ovarian Carcinoma Is Involved in the Development of Venous Thromboembolism
  1. Manabu Sakurai, MD,
  2. Koji Matsumoto, MD, PhD,
  3. Masahiko Gosho, PhD,
  4. Akiko Sakata, MD,
  5. Yoshihiko Hosokawa, MD,
  6. Yuri Tenjimbayashi, MD,
  7. Takashi Katoh, MD,
  8. Ayumi Shikama, MD,
  9. Haruna Komiya, MD,
  10. Hiroo Michikami, MD,
  11. Nobutaka Tasaka, MD,
  12. Azusa Akiyama-Abe, MD,
  13. Sari Nakao, MD, PhD,
  14. Hiroyuki Ochi, MD, PhD,
  15. Mamiko Onuki, MD, PhD,
  16. Takeo Minaguchi, MD, PhD,
  17. Hiroyuki Yoshikawa, MD, PhD and
  18. Toyomi Satoh, MD, PhD
  1. * Faculty of Medicine, Departments of Obstetrics and Gynecology and
  2. Clinical Trial and Clinical Epidemiology, and
  3. Department of Pathology, Tsukuba Human Tissue Diagnostic Center, University of Tsukuba, Tsukuba, Japan.
  1. Address correspondence and reprint requests to Manabu Sakurai, MD, Faculty of Medicine, Department of Obstetrics and Gynecology, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki 305-8575, Japan. E-mail: m-sakurai{at}


Objectives Our 2007 study of 32 patients with ovarian cancer reported the possible involvement of tissue factor (TF) in the development of venous thromboembolism (VTE) before treatment, especially in clear cell carcinoma (CCC). This follow-up study further investigated this possibility in a larger cohort.

Methods We investigated the intensity of TF expression (ITFE) and other variables for associations with VTE using univariate and multivariate analyses in 128 patients with epithelial ovarian cancer initially treated between November 2004 and December 2010, none of whom had received neoadjuvant chemotherapy. Before starting treatment, all patients were ultrasonographically screened for VTE. The ITFE was graded based on immunostaining of surgical specimens.

Results Histological types were serous carcinoma (n = 42), CCC (n = 12), endometrioid carcinoma (n = 15), mucinous carcinoma (n = 53), and undifferentiated carcinoma (n = 6). The prevalence of VTE was significantly higher in CCC (34%) than in non-CCC (17%, P = 0.03). As ITFE increased, the frequencies of CCC and VTE increased significantly (P < 0.001 and P = 0.014, respectively). Multivariate analysis identified TF expression and pretreatment dimerized plasmin fragment D level as significant independent risk factors for VTE development. These factors showed particularly strong impacts on advanced-stage disease (P = 0.021).

Conclusions The 2007 cohort was small, preventing multivariate analysis. This study of a larger cohort yielded stronger evidence that the development of VTE in epithelial ovarian cancer may involve TF expression in cancer tissues.

  • Tissue factor
  • Venous thromboembolism
  • Epithelial ovarian cancer

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  • The authors declare no conflicts of interest.