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

Int J Cancer. 2017 Feb 15;140(4):914-921. doi: 10.1002/ijc.30498. Epub 2016 Nov 14.

Abstract

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.

Keywords: D-dimer; coagulation; melanoma; thrombosis; tumor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers
  • Biomarkers, Tumor / blood
  • C-Reactive Protein / analysis
  • Disease-Free Survival
  • Female
  • Fibrin Fibrinogen Degradation Products / analysis*
  • Humans
  • Kaplan-Meier Estimate
  • L-Lactate Dehydrogenase / blood
  • Male
  • Melanoma / blood*
  • Melanoma / complications
  • Melanoma / mortality
  • Melanoma / pathology
  • Middle Aged
  • Neoplasm Invasiveness
  • Neovascularization, Pathologic / blood
  • Neovascularization, Pathologic / etiology
  • Prognosis
  • Proportional Hazards Models
  • Retrospective Studies
  • S100 Calcium Binding Protein beta Subunit / blood
  • Skin Neoplasms / blood*
  • Skin Neoplasms / complications
  • Skin Neoplasms / mortality
  • Skin Neoplasms / pathology
  • Thrombophilia / blood
  • Thrombophilia / etiology
  • Young Adult

Substances

  • Biomarkers
  • Biomarkers, Tumor
  • Fibrin Fibrinogen Degradation Products
  • S100 Calcium Binding Protein beta Subunit
  • S100B protein, human
  • fibrin fragment D
  • C-Reactive Protein
  • L-Lactate Dehydrogenase