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International Journal of Colorectal Disease

Erschienen in:

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

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

Erschienen in: International Journal of Colorectal Disease | Ausgabe 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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Titel: Association between increased tumor necrosis factor alpha levels and acquired activated protein C resistance in patients with metastatic colorectal cancer
verfasst von: Patrizia Ferroni
Silvia Riondino
Ilaria Portarena
Vincenzo Formica
Francesca La Farina
Francesca Martini
Gioia Massimiani
Raffaele Palmirotta
Fiorella Guadagni
Mario Roselli
Publikationsdatum: 01.12.2012
Verlag: Springer-Verlag
Erschienen in: International Journal of Colorectal Disease / Ausgabe 12/2012
Print ISSN: 0179-1958
Elektronische ISSN: 1432-1262
DOI: https://doi.org/10.1007/s00384-012-1493-8

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Abstract

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Methods

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Conclusions

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