Bache et al. BMC Cancer 2010, 10:132 http://www.biomedcentral.com/1471-2407/10/132 R E S E A R C H A R T I C L E Open Access Elevated tumor and serum levels of the hypoxia- associated protein osteopontin are associated with prognosis for soft tissue sarcoma patients Matthias Bache1*, Matthias Kappler1, Henri Wichmann1, Swetlana Rot1, Antje Hahnel1, Thomas Greither2, Harun M Said3, Matthias Kotzsch4, Peter Würl5, Helge Taubert2, Dirk Vordermark1 Abstract Background: Osteopontin (OPN) overexpression is correlated with a poor prognosis for tumor patients. However, only a few studies investigated the prognostic impact of expression of OPN in soft tissue sarcomas (STS) yet. Methods: This study is based on tumor and serum samples from 93 adult STS patients. We investigated OPN protein levels in serum (n = 86) and tumor tissue (n = 80) by ELISA and OPN mRNA levels in tumor tissue (n = 68) by quantitative real-time PCR. Results: No correlation was found between OPN levels in serum and tumor tissue. Moreover, an elevated OPN protein level in the serum was significantly associated with clinical parameters such as higher stage (p = 0.004), higher grade (p = 0.003), subtype (p = 0.002) and larger tumor size (p = 0.03). OPN protein levels in the tumor tissue were associated with higher stage (p = 0.06), higher grade (p = 0.003), subtype (p = 0.07) and an increased rate of relapse (p = 0.02). In addition, using a Cox’s proportional hazards regression model, we found that an elevated OPN protein level in the serum and tumor tissue extracts is a significant negative prognostic factor for patients with STS. The relative risks of tumor-related death were 2.2 (p < 0.05) and 3.7 (p = 0.01), respectively. Conclusion: Our data suggest OPN protein in serum as well as in tumor tissue extracts is an important prognostic factor for soft tissue sarcoma patients. Background OPN, a phosphorylated glycoprotein, is detected in body fluids as well as in tumor tissues. Initially, it was sug- gested that OPN is expressed by macrophages infiltrat- ing the tumor rather than by tumor cells themselves [1]. However, elevated serum or plasma levels of OPN have been detected in a variety of human cancers, which has been correlated with tumor progression and metastasis [2-4]. Moreover, tumor OPN protein over expression is also linked to a worse prognosis in different tumor enti- ties such as breast cancer [5,6], lung cancer [7], cervical cancer [8,9], prostate cancer [10] and head and neck cancer [11-13]. Furthermore, previous studies suggest that high tumor OPN mRNA expression also correlates with an unfavorable prognosis [14-18]. * Correspondence: matthias.bache@medizin.uni-halle.de 1Department of Radiotherapy, Martin-Luther-University Halle-Wittenberg, Halle, Germany In support of its prognostic value, direct or indirect inhibition of the OPN signaling pathway results in reduced malignant tumor potential with effects on cell survival, migration, invasion, tumor growth and metasta- sis (reviewed in [4,19,20]). However, only a few studies have investigated the role of osteopontin in tumor pro- gression of sarcoma patients. For example, in primary sarcomas of the pulmonary artery, OPN protein could be detected in tumor cells and in macrophages and it is potentially involved in tumor progression and metastasis [21]. A further immunohistochemical study of STS showed that OPN in tumor tissue is associated with tumor stage, grade and overall survival of STS patients at 5-years [22]. However, another study using immuno- histochemical evaluation of OPN expression did not provide predictive information on the outcome of osteo- sarcoma patients [23]. We therefore analyzed OPN mRNA and protein levels of tumor samples and OPN © 2010 Bache et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.