D-dimers in malignant melanoma: Association with prognosis and dynamic variation in disease progress.
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.
Experimental Dermatology, Department of Dermatology, Venereology, and Allergology, University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, Mannheim, Germany.
Anna
A
Desch
Department of Dermatology, Venereology, and Allergology, University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, Mannheim, Germany.|Skin Cancer Unit, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Christoffer
C
Gebhardt
Department of Dermatology, Venereology, and Allergology, University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, Mannheim, Germany.|Skin Cancer Unit, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Jochen
J
Utikal
Department of Dermatology and Venerology, University Hospital Hamburg-Eppendorf, Hamburg, Germany.
Stefan W
SW
Schneider
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers; D014408:Biomarkers, Tumor / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis; D018572:Disease-Free Survival; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis*; D006801:Humans; D053208:Kaplan-Meier Estimate; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008297:Male; D008545:Melanoma / Q000097:blood* / Q000150:complications / Q000401:mortality / Q000473:pathology; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009389:Neovascularization, Pathologic / Q000097:blood / Q000209:etiology; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D064568:S100 Calcium Binding Protein beta Subunit / Q000097:blood; D012878:Skin Neoplasms / Q000097:blood* / Q000150:complications / Q000401:mortality / Q000473:pathology; D019851:Thrombophilia / Q000097:blood / Q000209:etiology; D055815:Young Adult
D015415:Biomarkers; D014408:Biomarkers, Tumor; D005338:Fibrin Fibrinogen Degradation Products; D064568:S100 Calcium Binding Protein beta Subunit; C579160:S100B protein, human; C036309:fibrin fragment D; D002097:C-Reactive Protein; D007770:L-Lactate Dehydrogenase
D-dimer; coagulation; melanoma; thrombosis; tumor