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Breast Cancer Research
Published in: Breast Cancer Research 1/2015

Open Access 01-12-2015 | Research article

Tumor expression, plasma levels and genetic polymorphisms of the coagulation inhibitor TFPI are associated with clinicopathological parameters and survival in breast cancer, in contrast to the coagulation initiator TF

Authors: Mari Tinholt, Hans Kristian Moen Vollan, Kristine Kleivi Sahlberg, Sandra Jernström, Fatemeh Kaveh, Ole Christian Lingjærde, Rolf Kåresen, Torill Sauer, Vessela Kristensen, Anne-Lise Børresen-Dale, Per Morten Sandset, Nina Iversen

Published in: Breast Cancer Research | Issue 1/2015

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Abstract

Introduction

Hypercoagulability in malignancy increases the risk of thrombosis, but is also involved in cancer progression. Experimental studies suggest that tissue factor (TF) and tissue factor pathway inhibitor (TFPI) are involved in cancer biology as a tumor- promoter and suppressor, respectively, but the clinical significance is less clear. Here, we aimed to investigate the clinical relevance of TF and TFPI genetic and phenotypic diversity in breast cancer.

Methods

The relationship between tumor messenger RNA (mRNA) expression and plasma levels of TF and TFPI (α and β), tagging single nucleotide polymorphisms (tagSNPs) in F3 (TF) (n = 6) and TFPI (n = 18), and clinicopathological characteristics and molecular tumor subtypes were explored in 152 treatment naive breast cancer patients. The effect of tumor expressed TF and TFPIα and TFPIβ on survival was investigated in a merged breast cancer dataset of 1881 patients.

Results

Progesterone receptor negative patients had higher mRNA expression of total TFPI (α + β) (P = 0.021) and TFPIβ (P = 0.014) in tumors. TF mRNA expression was decreased in grade 3 tumors (P = 0.003). In plasma, total TFPI levels were decreased in patients with larger tumors (P = 0.013). SNP haplotypes of TFPI, but not TF, were associated with specific clinicopathological characteristics like tumor size (odds ratio (OR) 3.14, P = 0.004), triple negativity (OR 2.4, P = 0.004), lymph node spread (OR 3.34, P = 0.006), and basal-like (OR 2.3, P = 0.011) and luminal B (OR 3.5, P = 0.005) molecular tumor subtypes. Increased expression levels of TFPIα and TFPIβ in breast tumors were associated with better outcome in all tumor subtypes combined (P = 0.007 and P = 0.005) and in multiple subgroups, including lymph node positive subjects (P = 0.006 and P = 0.034).

Conclusions

This study indicates that genetic and phenotypic variation of both TFPIα and TFPIβ, more than TF, are markers of cancer progression. Together with the previously demonstrated tumor suppressor effects of TFPI, the beneficial effect of tumor expressed TFPI on survival, renders TFPI as a potential anticancer agent, and the clinical significance of TFPI in cancer deserves further investigation.
Appendix
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Metadata
Title
Tumor expression, plasma levels and genetic polymorphisms of the coagulation inhibitor TFPI are associated with clinicopathological parameters and survival in breast cancer, in contrast to the coagulation initiator TF
Authors
Mari Tinholt
Hans Kristian Moen Vollan
Kristine Kleivi Sahlberg
Sandra Jernström
Fatemeh Kaveh
Ole Christian Lingjærde
Rolf Kåresen
Torill Sauer
Vessela Kristensen
Anne-Lise Børresen-Dale
Per Morten Sandset
Nina Iversen
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 1/2015
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/s13058-015-0548-5

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