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Published in: International Journal of Colorectal Disease 12/2012

01-12-2012 | Original Article

Association between increased tumor necrosis factor alpha levels and acquired activated protein C resistance in patients with metastatic colorectal cancer

Authors: Patrizia Ferroni, Silvia Riondino, Ilaria Portarena, Vincenzo Formica, Francesca La Farina, Francesca Martini, Gioia Massimiani, Raffaele Palmirotta, Fiorella Guadagni, Mario Roselli

Published in: International Journal of Colorectal Disease | Issue 12/2012

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Abstract

Purpose

The purpose of this study was to investigate the possible association between tumor necrosis factor-α (TNF-α) levels and defects in the activated protein C (APC) system as a determinant of venous thromboembolism (VTE) in metastatic colorectal cancer patients (mCRC) undergoing chemotherapy.

Methods

TNF-α levels (measured by immunoassay) and abnormalities in the APC system [evaluated by an APC-dependent thrombin generation assay (ThromboPath—ThP)] were evaluated in 45 mCRC patients undergoing chemotherapy. VTE events were recorded during follow-up.

Results

TNF-α levels were increased (p < 0.01), and APC functionality was decreased (p < 0.0001) in mCRC patients compared to age- and sex-matched controls. An inverse correlation was observed between TNF-α and APC impairment in mCRC (p < 0.0001). TNF-α was confirmed as an independent predictor (p = 0.007) for APC abnormalities at multivariate regression analysis. Nine (20 %) of 45 mCRC patients experienced VTE during chemotherapy. Bayesian analysis of combined ThP/TNF-α showed a positive predictive value of 0.67 in predicting VTE (p = 0.01). Cox proportional hazards survival analysis confirmed the predictive value of combined ThP/TNF-α determination in VTE risk assessment of mCRC patients (either negative vs. both positive: HR = 0.02; p = 0.001), and Kaplan–Meier analysis demonstrated that mCRC patients with either negative TNF-α or ThP values prior to chemotherapy were less likely to experience VTE (13 %) than patients with abnormalities of both markers (67 %, p = 0.002).

Conclusions

These results suggest that the host inflammatory response to cancer cells and/or tumor-derived cytokines could be responsible for an impairment of the APC system and a switch toward a pro-thrombotic state, which might predispose to the occurrence of VTE in mCRC patients undergoing chemotherapy.
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Metadata
Title
Association between increased tumor necrosis factor alpha levels and acquired activated protein C resistance in patients with metastatic colorectal cancer
Authors
Patrizia Ferroni
Silvia Riondino
Ilaria Portarena
Vincenzo Formica
Francesca La Farina
Francesca Martini
Gioia Massimiani
Raffaele Palmirotta
Fiorella Guadagni
Mario Roselli
Publication date
01-12-2012
Publisher
Springer-Verlag
Published in
International Journal of Colorectal Disease / Issue 12/2012
Print ISSN: 0179-1958
Electronic ISSN: 1432-1262
DOI
https://doi.org/10.1007/s00384-012-1493-8

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