Expression of Tissue Factor in Epithelial Ovarian Carcinoma Is Involved in the Development of Venous Thromboembolism

Abstract

ObjectivesOur 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.MethodsWe 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.ResultsHistological 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).ConclusionsThe 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.

Prevalence of venous thromboembolism at pretreatment screening and associated risk factors in 2086 patients with gynecological cancer

“…In patients who have developed asymptomatic VTE prior to treatment, iatrogenic symptomatic PE may be induced intraoperatively or postoperatively when prolonged or highly invasive surgery is performed, or when intermittent pneumatic compression is applied to patients without being aware of the presence of VTE. Factors involved in the occurrence of VTE in cancer patients before treatment include: congenital predisposition to thrombophilia, vein displacement caused by the tumor and hemoconcentration due to ascites production, as well as the potential activation of the extrinsic coagulation pathway by tumor‐produced tissue factor (TF) in ovarian cancer, as shown previously by our group . It has been reported that the pre‐treatment prevalence of VTE in patients with gynecological malignant tumors is 2.8–4.8% in cervical cancer, 5.1–9.9% in endometrial cancer and 7.1–26.7% in ovarian cancer, indicating that asymptomatic cases are common.…”

“…Massive ascites was also likely identified due to hemoconcentration caused by intravascular dehydration, in addition to the direct compression applied to veins by the ascites. Clear cell carcinoma was identified as an independent and significant risk factor, possibly because clear cell carcinoma has significantly higher TF expression compared to other histological types, indicating that the extrinsic coagulation pathway may be accelerated. Additionally, stage III/IV advanced cancer, LN enlargement that suggests metastasis and tumor extension beyond the primary organ were identified as independent and significant risk factors for pretreatment VTE, and this may be a consequence of augmentation in blood coagulation through basement membrane destruction and interstitial infiltration caused by tumor extension/metastasis and stimulation from and the immune response to intravascular/intraductal entry .…”

Risk factors for deep venous thrombosis in women with ovarian cancer

“…Recent study demonstrated that TF was involved in the pretreatment development of VTE in ovarian cancer, particularly in CCC. [ 19 ]…”

The role of tissue factor in metastasising, neoangiogenesis and hemostasis in cancer

“…В частности, известно, что при онкологических заболеваниях TF задействован в росте, неоваскуляризации и метастазировании злокачественных опухолей [11]. Кроме этого, существует большое количество экспериментальных данных, подтверждающих, что TF играет роль в развитии тромбозов (в частности, венозной тромбоэмболии (ВТ) и тромбоза глубоких вен (ТГВ)) у пациентов с онкологическими заболеваниями [12,13].…”

“…тканевый фактор и нарушения системы гемостаза. Как показали результаты иммуногистохимических исследований, для пациентов с карциномой яичников [13] риск развития ВТ / ТГВ выше в случае высокой экспрессии TF опухолевыми клетками.…”