D-dimers in malignant melanoma: Association with prognosis and dynamic variation in disease progress

TY - JOUR

T1 - D-dimers in malignant melanoma: Association with prognosis and dynamic variation in disease progress

AU - Desch, Anna

AU - Gebhardt, Christoffer

AU - Utikal, Jochen

AU - Schneider, Stefan W

N1 - © 2016 UICC.

PY - 2017/2/15

Y1 - 2017/2/15

N2 - Malignant cells elicit a chronic hemostatic activation in disease progress. This procoagulant activity does not only bear a risk for thromboembolism but also facilitates tumor growth and dissemination. An elevated plasma D-dimer level indicates an activated coagulation and fibrinolysis. In this study, the association of D-dimer levels with clinicopathological parameters and patients outcome in melanoma was investigated analyzing in total 533 melanoma patients retrospectively. Using the cut-off point of 0.6 mg/L D-dimer 145 of the total 533 patients (27.2%) were identified with elevated plasma D-dimer levels. This increased D-dimer level positively correlated with tumor thickness (p = 0.0003), lymph node invasion (p = 0.0004) and metastatic state (p <0.0001). To assess the association of D-dimer levels with progression-free survival (PFS) and overall survival (OS), long-rank test and the Cox proportional hazard model was performed. Univariate analyses revealed that elevated D-dimer levels were significantly associated with decreased PFS (HR:2.89, 95% CI (2.07-7.56), p < 0.0001) and OS (HR:2.22, 95% CI (1.06-4.57), p = 0.035). Moreover, multivariate analyses identified elevated D-dimer levels being associated with poor disease outcome (PFS:HR:2.47, 95% CI (1.23-4.98), p = 0.012; OS:HR:2.01, 95% CI (0.09-4.45), p = 0.087). Additionally, D-dimer levels were significantly increased in terminal stage patients when comparing plasma levels 0-8 versus 24-48 weeks before death (p = 0.0003). In summary, this study presents multiple evidence that elevated D-dimer levels in melanoma patients associate with poor prognosis and therefore plasma levels of D-dimers could reveal a more aggressive phenotype of melanoma and may guide the management of anti-melanoma treatment including the concept of an anti-coagulatory therapy in tumor patients.

AB - Malignant cells elicit a chronic hemostatic activation in disease progress. This procoagulant activity does not only bear a risk for thromboembolism but also facilitates tumor growth and dissemination. An elevated plasma D-dimer level indicates an activated coagulation and fibrinolysis. In this study, the association of D-dimer levels with clinicopathological parameters and patients outcome in melanoma was investigated analyzing in total 533 melanoma patients retrospectively. Using the cut-off point of 0.6 mg/L D-dimer 145 of the total 533 patients (27.2%) were identified with elevated plasma D-dimer levels. This increased D-dimer level positively correlated with tumor thickness (p = 0.0003), lymph node invasion (p = 0.0004) and metastatic state (p <0.0001). To assess the association of D-dimer levels with progression-free survival (PFS) and overall survival (OS), long-rank test and the Cox proportional hazard model was performed. Univariate analyses revealed that elevated D-dimer levels were significantly associated with decreased PFS (HR:2.89, 95% CI (2.07-7.56), p < 0.0001) and OS (HR:2.22, 95% CI (1.06-4.57), p = 0.035). Moreover, multivariate analyses identified elevated D-dimer levels being associated with poor disease outcome (PFS:HR:2.47, 95% CI (1.23-4.98), p = 0.012; OS:HR:2.01, 95% CI (0.09-4.45), p = 0.087). Additionally, D-dimer levels were significantly increased in terminal stage patients when comparing plasma levels 0-8 versus 24-48 weeks before death (p = 0.0003). In summary, this study presents multiple evidence that elevated D-dimer levels in melanoma patients associate with poor prognosis and therefore plasma levels of D-dimers could reveal a more aggressive phenotype of melanoma and may guide the management of anti-melanoma treatment including the concept of an anti-coagulatory therapy in tumor patients.

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Biomarkers

KW - Biomarkers, Tumor

KW - C-Reactive Protein

KW - Disease-Free Survival

KW - Female

KW - Fibrin Fibrinogen Degradation Products

KW - Humans

KW - Kaplan-Meier Estimate

KW - L-Lactate Dehydrogenase

KW - Male

KW - Melanoma

KW - Middle Aged

KW - Neoplasm Invasiveness

KW - Neovascularization, Pathologic

KW - Prognosis

KW - Proportional Hazards Models

KW - Retrospective Studies

KW - S100 Calcium Binding Protein beta Subunit

KW - Skin Neoplasms

KW - Thrombophilia

KW - Young Adult

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1002/ijc.30498

DO - 10.1002/ijc.30498

M3 - SCORING: Journal article

C2 - 27813063

VL - 140

SP - 914

EP - 921

JO - INT J CANCER

JF - INT J CANCER

SN - 0020-7136

IS - 4

ER -