PB0931 - Mechanisms of cancer associated thrombosis in gynaecological cancer patients-tumour or treatment effect?

Monday, July 11, 2022

6:30 PM – 7:30 PM

Location: Exhibition

Presentation Format: In-Person

Co-Author(s)

MW

Mark P. Ward

Molecular Scientist
Dept Histopathology, Trinity St. James's Cancer Institute, St. James's Hospital, Dublin 8 Ireland
Dublin 8, Dublin, Ireland
SO

Sharon A. O'Toole

Senior Research Fellow
Dept of Histopathology & Dept of Obstetrics and Gynaecology, Trinity St. James's Cancer Institute, St. James's Hospital, Dublin 8
Dublin, Dublin, Ireland
FA

Feras Abu Saadeh

Consultant Gynae-oncologist
Dept of Gynae-Oncology, Trinity St. James's Cancer Institute, Dublin 8, Ireland
Dublin, Dublin, Ireland
ZM

Zibi Marchocki

Gynae-oncologist
Dept of Gynae-Oncology, Trinity St. James's Cancer Institute, St. James's Hospital, Dublin 8, Ireland
Dublin, Dublin, Ireland
EI

Elzahra M. Ibrahim

Gynae-oncologist
Dept of Gynae-Oncology, Trinity St. James's Cancer Institute, St. James's Hospital, Dublin 8
Dublin, Dublin, Ireland
FM

Fiona Martin

Post doctoral research fellow
Dept of Obstetrics and Gynaecology, Trinity St. James's Cancer Institute, Dublin 8, Ireland
Dublin, Dublin, Ireland
NG

Noreen Gleeson

Associate Professor
Dept of Gynae-oncology, Trinity St. James's Cancer Institute, St. James's Hospital, Dublin 8
Dublin, Dublin, Ireland
JO

John J. O'Leary

Professor
Dept of Histopathology, Trinity St. James Cancer Institute, St. James's Hospital, Dublin 8
Dublin, Dublin, Ireland

Presenting Author(s)

Lucy A. Norris, PhD

Senior Scientist
Trinity St. James's Institute,
Dublin 8, Dublin, Ireland

Background: Gynaecological cancers patients are at high risk of venous thromboembolism(VTE) however the mechanism by which VTE occurs is not understood and could be tumour or treatment related.

Aims: The aim of this study is to determine the mechanism of hypercoagulability in gynaecological cancer patients and to assess the role of tumour and treatment factors in the enhanced thrombin generation observed in patients who subsequently develop VTE.

Methods: mRNA expression of Prothrombin(F2), Tissue Factor(TF), Tissue Factor Pathway Inhibitor -1(TFPI-1), TFPI-2, endothelial protein C receptor(EPCR), protein S(PS), protein C (PC), thrombomodulin (TM), Factor V (FV) and VIII (FVIII) was measured in tumour biopsies from 26 treatment naïve gynaecological cancer patients who developed VTE compared with matched controls. Plasma levels of FV, F8, TFPI, TM, PS, EPCR were determined by ELISA and were correlated with thrombin generation(ETP) in patients who subsequently developed VTE (VTE group). Ethical approval and informed consent was obtained.

Results: No significant differences in tumour mRNA expression was observed in patients who developed VTE compared with those who remained thrombosis free. In treatment naïve patients, pre-operative ETP and Factor VIII were significantly increased in patients who developed VTE(VTE group) compared with matched controls(Non VTE group)(P < 0.05;P < 0.03). FVIII correlated with peak thrombin levels in the VTE group (r=0.560). In patients treated with neoadjuvant chemotherapy before surgery, TM was reduced in the VTE group compared with the non VTE group(P < 0.03). TM correlated negatively with ETP in the VTE group(r=-4558).

Conclusion(s): Tumour expression of coagulation proteases does not appear to be implicated in VTE in gynaecological cancer patients. FVIII levels contribute to the pro-coagulant activity observed in treatment naive gynaecological cancer patients who develop VTE. Reduced levels of TM may be linked to chemotherapy associated endothelial damage and result in impaired activation of protein C at the endothelial surface resulting in chemotherapy associated VTE.