Prognostic relevance of increased angiogenesis in osteosarcoma.

9022 Background: Osteosarcoma, the most frequent primary malignant bone tumor is a chemotherapy-sensitive tumor with survival rates reaching 50 to 80 %. Several reports have demonstrated that neovascularization assessed by intratumoral microvessel density (MVD) correlates with clinicopathological factors and the patients' prognosis in a variety of tumors. However, the role of angiogenesis in osteosarcoma still remains unclear. METHODS Pretherapeutic tumor biopsies of 60 patients with high grade central osteosarcoma, who were treated according to multimodal neoadjuvant protocols of the Cooperative German-Austrian-Swiss Osteosarcoma Study Group, were evaluated for intratumoral microvessel density. MVD was analyzed with regard to demographic and tumor-related variables, response, and survival. RESULTS The median intratumoral microvessel count was 52 (interquartile range 31-77). At a median follow up period of 1274 days patients with a high (≥ 53) MVD had significantly better 5- and 10-year overall survival rates with 84 % than patients with low (≤ 52) MVD with 49 % (p = 0.0029, Cox regression analysis). Furthermore a better relapse free survival for high MVD patients (p = 0.0064) was observed. In a subgroup analysis of 47 patients with primary high grade central osteosarcoma of the extremities without primary metastases, patients with high MVD showed significant better 5- and 10-year overall survival rates with 91 % versus 61 % for low MVD (p = 0,039). Cox regression analysis revealed that MVD was an independent prognostic factor for survival. A good response to chemotherapy (histological grading scale of Salzer-Kuntschik) correlated significantly with a high degree of MVD (r = 0.3; p = 0.033). CONCLUSIONS Increased angiogenesis is a prognostic indicator for better survival and response to chemotherapy in patients with osteosarcoma. Thus, determination of MVD might be useful in selecting patients for further neoadjuvant treatment decisions. [Table: see text].