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Open Access Research article

The VEGF- and PDGF-family of angiogenic markers have prognostic impact in soft tissue sarcomas arising in the extremities and trunk

Thomas K Kilvaer1*, Eivind Smeland1, Andrej Valkov23, Sveinung W Sorbye23, Roy M Bremnes14, Lill-Tove Busund23 and Tom Donnem14

Author Affiliations

1 Department of Oncology, University Hospital of North Norway, Tromso, 9037 Norway

2 Institute of Medical Biology, University of Tromso, Tromso, Norway

3 Department of Clinical Pathology, University Hospital of North Norway, Tromso, Norway

4 Institute of Clinical Medicine, University of Tromso, Tromso, Norway

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BMC Clinical Pathology 2014, 14:5  doi:10.1186/1472-6890-14-5

Published: 20 January 2014

Abstract

Background

Soft-tissue sarcomas are rare malignant tumors of mesenchymal lineage that can arise in any part of the body. Prognosis, and hence also treatment may vary according to histologic subtype and localization. Angiogenesis is the process of forming new blood vessels from pre-existing ones. The deregulation of this process is thought to be an important step in malignant transformation. This study investigates the prognostic impact of platelet derived growth factor- (PDGF), vascular endothelial growth factor- (VEGF) and fibroblast growth factor (FGF) families in soft-tissue sarcomas of the extremities & trunk (ET) and visceral & retroperitoneal (VR) locations.

Methods

Tumor samples from 181 patients (115 ET and 66 VR) with resected soft tissue sarcomas were collected and tissue microarrays were constructed. Immunohistochemistry was used to evaluate angiogenic marker expression. Recurrence-free survival (RFS), metastasis-free survival (MFS) and disease-specific survival (DSS) were used as endpoints in prognostic impact assessment.

Results

In univariate analyses, almost all investigated angiogenic markers had prognostic impact in the ET group. In contrast, only FGFR-1 showed any significant prognostic impact in the VR group. In the multivariate analyses, PDGF-D (HR = 1.863, 95% CI = 1.057-3.283, P = 0.031), VEGFR-1 (HR = 2.106, 95% CI = 1.038-4.272, P = 0.039) and VEGF-A (HR 2.095, 95% CI 1.028-4.271, P = 0.042) were independent negative prognosticators for DSS, MFS and RFS, respectively, in the ET group. FGFR-1 was an independent positive prognosticator for DSS (HR = 0.243, 95% CI = 0.095-0.618, P = 0.003) in the VR group.

Conclusions

Angiogenic molecules from the PDGF and VEGF families have prognostic impact in soft-tissue sarcomas arising in the ET, but not in VR locations. In the latter histological grade and resection margins are the most important prognostic factors.

Keywords:
Angiogenesis; Sarcoma; Extremity; Trunk; FGF; PDGF; VEGF; Visceral; Retroperitoneal