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

Thomas K Kilvaer,Andrej Valkov,Sveinung W Sorbye,Eivind Smeland,Roy M Bremnes,Lill-Tove Busund,Tom Donnem

doi:10.1186/1472-6890-14-5

Thomas K Kilvaer, Andrej Valkov + Show 5 more

Open Access

https://doi.org/10.1186/1472-6890-14-5

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Abstract

BackgroundSoft-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.MethodsTumor 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.ResultsIn 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.ConclusionsAngiogenic 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.

Highlights

Soft-tissue sarcomas are rare malignant tumors of mesenchymal lineage that can arise in any part of the body
platelet derived growth factor- (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 vascular endothelial growth factor- (VEGF)-A
(HR 2.095, 95% CI 1.028-4.271, P = 0.042) were independent negative prognosticators for disease-specific survival (DSS), metastasis-free survival (MFS) and Recurrence-free survival (RFS), respectively, in the extremities & trunk (ET) group

Summary

Introduction

Soft-tissue sarcomas are rare malignant tumors of mesenchymal lineage that can arise in any part of the body. Soft tissue sarcomas (STS) constitute a highly heterogeneous collection of tumors comprising over 50 histological subtypes, arising from mesenchymal tissue and capable of forming tumors in all parts of the human body [1]. This group amounts to 0.5-1% of the annual tumor burden with a mortality of about 40-60%, resulting in an estimated. It is good practice to distinguish between STSs arising in the extremity & trunk (ET), head & neck (HN) and visceral & retroperitoneal (VR) localizations as treatment and prognosis vary widely according to localization [3]. Adjuvant chemotherapy for adult STS is still under investigation, and the routine use of such treatment is today limited to the palliative setting [5]

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