Pre-surgical level of von Willebrand factor as an evident indicator of breast cancer recurrence

BACKGROUND: Endothelial and platelet activation as well as a disruption of haemostatic balance are crucial in cancer-dependent venous thromboembolism development. OBJECTIVE: The aim of this study was to investigate the influence of von Willebrand factor (VWF), sE-selectin, sP-selectin as well as VWF/sE-selectin and sP-selectin/sE-selectin ratios on the probability of disease relapse in invasive breast carcinoma (IBrC) cases. METHODS: Eighty-four patients with IA-IIB stage of IBrC who passed a comprehensive clinicopathologic evaluation were included in the study. Follow-up was completed in all patients with a 15.48 % recurrence rate. An immunoassay of VWF antigen, sE-selectin, sP-selectin, as well as an immunohistochemistry of oestrogen and progesterone receptors, human epidermal growth factor receptor 2 (HER2) and Ki67 was performed in all cases. RESULTS: The VWF/sE-selectin ratio was significantly higher in patients with poorly differentiated tumours than in those with high-differentiated tumours. A positive correlation between VWF concentration and tumour grade was noted. Eleven of 13 events happened in patients with VWF value below 600 mU/mL with recurrence rate of 25%, but only two events occurred in subject with VWF values above the 600 mU/mL (5%; P= 0.0028). CONCLUSIONS: Our study show that VWF could be considered as a suitable biomarker of breast cancer relapse.

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The role of von Willebrand factor in breast cancer metastasis

Translational Oncology ◽

10.1016/j.tranon.2021.101033 ◽

2021 ◽

Vol 14 (4) ◽

pp. 101033

Author(s):

Chia Yin Goh ◽

Sean Patmore ◽

Albert Smolenski ◽

Jane Howard ◽

Shane Evans ◽

...

Keyword(s):

Breast Cancer ◽

Von Willebrand Factor ◽

Cancer Metastasis ◽

Breast Cancer Metastasis ◽

Von Willebrand ◽

Willebrand Factor

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VON WILLEBRAND FACTOR, ANGIODYSPLASIA AND ANGIOGENESIS

Mediterranean Journal of Hematology and Infectious Diseases ◽

10.4084/mjhid.2013.060 ◽

2013 ◽

Vol 5 (1) ◽

pp. e2013060 ◽

Cited By ~ 56

Author(s):

Anna M. Randi ◽

Mike A Laffan ◽

Richard D. Starke

Keyword(s):

Von Willebrand Factor ◽

Growth Factor Receptor ◽

Integrin Αvβ3 ◽

Von Willebrand Disease ◽

Clinical Implications ◽

Vascular Endothelial ◽

Angiopoietin 2 ◽

Von Willebrand ◽

Endothelial Growth Factor ◽

Willebrand Factor

The large multimeric glycoprotein Von Willebrand factor (VWF) is best known for its role in haemostasis; however in recent years other functions of VWF have been identified, indicating that this protein is involved in multiple vascular processes. We recently described a new role for VWF in controlling angiogenesis, which may have significant clinical implications for patients with Von Willebrand disease (VWD), a genetic or acquired condition caused by the deficiency or dysfunction of VWF. VWD can be associated with angiodysplasia, a condition of degenerative blood vessels often present in the gastrointestinal tract, linked to dysregulated angiogenesis. Angiodysplasia can cause severe intractable bleeding, often refractory to conventional VWD treatments. In this review summarise the evidence showing that VWF controls angiogenesis, and review the angiogenic pathways which have been implicated in this process. We discuss the possible mechanisms though which VWF regulates angiopoietin-2 (Ang-2) and integrin αvβ3, leading to signalling through vascular endothelial growth factor receptor-2 (VEGFR2), one of the most potent activators of angiogenesis. We also review the evidence that links VWF with angiodysplasia, and how the newly identified function of VWF in controlling angiogenesis may pave the way for the development of novel therapies for the treatment of angiodysplasia in congenital VWD and in acquired conditions such as Heyde syndrome.

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Quantifying tumour vascularity in non-luminal breast cancers

Journal of Clinical Pathology ◽

10.1136/jclinpath-2016-204208 ◽

2017 ◽

Vol 70 (9) ◽

pp. 766-774 ◽

Cited By ~ 4

Author(s):

Maria Ryssdal Kraby ◽

Signe Opdahl ◽

Lars A Akslen ◽

Anna M Bofin

Keyword(s):

Breast Cancer ◽

Growth Factor Receptor ◽

Proliferation Index ◽

Breast Cancers ◽

Basal Phenotype ◽

Vascular Proliferation ◽

Tumour Vascularity ◽

Epidermal Growth ◽

Von Willebrand ◽

Willebrand Factor

AimsMicrovessel density (MVD), proliferating MVD (pMVD) and vascular proliferation index (VPI) are methods used to quantify tumour vascularity in histopathological sections. In this study, we assessed MVD, pMVD and VPI in non-luminal subtypes of breast cancer. Differences between subtypes were studied, and the prognostic value of each method was assessed.MethodsAll non-luminal subtypes (61 basal phenotype (BP), 60 human epidermal growth factor receptor 2 (HER2) type and 30 five negative phenotype (5NP)) were selected from a series comprising 909 cases of breast cancer. Sections were stained for Ki67 and von Willebrand factor. Associations between MVD, pMVD and VPI, molecular subtypes and prognosis were studied.ResultsMVD was highest in 5NP (Δ54.3 microvessels/mm2compared with BP, 95% CI 30.3 to 78.3), whereas no clear difference was found between HER2 type and BP (Δ8.8 microvessels/mm2, 95% CI −9.6 to 27.1). pMVD and VPI did not differ between subtypes. For MVD, HR was 1.07 (95% CI 1.03 to 1.11) per 10 vessel increase and 1.9 (95% CI 1.2 to 3.1) if MVD was greater than median value. High MVD was associated with poor prognosis in the HER2 type (HR 1.07 (95% CI 1.02 to 1.12)) and 5NP (HR 1.13 (95% CI 1.03 to 1.23)), but not in BP (HR 1.04 (95% CI 0.94 to 1.14) per 10 vessel increase). pMVD and VPI were not associated with prognosis.ConclusionsMVD appears to be an independent prognostic factor in HER2 and 5NP subtypes of breast cancer, where high MVD is associated with poor survival. MVD was higher in the 5NP compared with both BP and HER2 type.

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Increased soluble P-selectin in patients with haematological and breast cancer: a comparison with fibrinogen, plasminogen activator inhibitor and von Willebrand factor

Blood Coagulation & Fibrinolysis ◽

10.1097/00001721-200101000-00007 ◽

2001 ◽

Vol 12 (1) ◽

pp. 43-50 ◽

Cited By ~ 60

Author(s):

A. D. Blann ◽

D. Gurney ◽

M. Wadley ◽

D. Bareford ◽

P. Stonelake ◽

...

Keyword(s):

Breast Cancer ◽

Plasminogen Activator ◽

Von Willebrand Factor ◽

Plasminogen Activator Inhibitor ◽

Soluble P ◽

Von Willebrand ◽

Willebrand Factor ◽

Activator Inhibitor

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Differential expression of sushi, von Willebrand factor type A, EGF and pentraxin domain-containing 1 in cancers of the breast.

10.31219/osf.io/8knq3 ◽

2021 ◽

Author(s):

Shahan Mamoor

Keyword(s):

Breast Cancer ◽

Differential Expression ◽

Von Willebrand Factor ◽

Type A ◽

Normal Breast ◽

Differentially Expressed ◽

Primary Tumors ◽

Factor Type ◽

Von Willebrand ◽

Willebrand Factor

Breast cancer affects women at relatively high frequency (1). We mined published microarray datasets (2, 3) to determine in an unbiased fashion and at the systems level genes most differentially expressed in the primary tumors of patients with breast cancer. We report here significant differential expression of the gene encoding sushi, von Willebrand factor type A, EGF and pentraxin domain-containing 1, SVEP1, when comparing primary tumors of the breast to the tissue of origin, the normal breast. SVEP1 was also differentially expressed in the brain metastases of patients with metastatic breast cancer. SVEP1 mRNA was present at significantly lower quantities in tumors of the breast as compared to normal breast tissue. Analysis of human survival data revealed that expression of SVEP1 in primary tumors of the breast was correlated with distant metastasis-free survival in patients with normal-like subtype cancer, demonstrating a relationship between primary tumor expression of a differentially expressed gene and patient survival outcomes influenced by PAM50 molecular subtype. SVEP1 may be of relevance to initiation, maintenance or progression of cancers of the female breast.

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