Joshua G Cohen1, Emily Prendergast2, Julia E Geddings3, Ann E Walts4, Hasmik Agadjanian2, Yohei Hisada5, Beth Y Karlan2, Nigel Mackman5, Christine S Walsh6. 1. Division of Gynecologic Oncology, University of California, Los Angeles, 200 Medical Plaza, Suite 220, Los Angeles, CA 90095, USA. 2. Division of Gynecologic Oncology, Cedars-Sinai Medical Center, 8635 West 3rd Street, Suite 280W, Los Angeles, CA 90048, USA. 3. Division of Hematology/Oncology, University of North Carolina, Chapel Hill, 2312 MBRB, 111 Mason Farm Rd, CB#7126, Chapel Hill, NC 27599, USA. 4. Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA 90048, USA. 5. Division of Hematology/Oncology, University of North Carolina, Chapel Hill, 2312 MBRB, 111 Mason Farm Rd, CB#7126, Chapel Hill, NC 27599, USA; K.G. Jebsen TREC, The Faculty of Health Sciences, UiT- The Arctic University of Tromsø, 9037 Tromsø, Norway. 6. Division of Gynecologic Oncology, Cedars-Sinai Medical Center, 8635 West 3rd Street, Suite 280W, Los Angeles, CA 90048, USA. Electronic address: Christine.Walsh@cshs.org.
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.
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.
Authors: Alok A Khorana; Nigel Mackman; Anna Falanga; Ingrid Pabinger; Simon Noble; Walter Ageno; Florian Moik; Agnes Y Y Lee Journal: Nat Rev Dis Primers Date: 2022-02-17 Impact factor: 65.038
Authors: Yohei Hisada; Kenison B Garratt; Anaum Maqsood; Steven P Grover; Tomohiro Kawano; Brian C Cooley; Jonathan Erlich; Florian Moik; Matthew J Flick; Ingrid Pabinger; Nigel Mackman; Cihan Ay Journal: Blood Adv Date: 2021-01-26