title: Prognostic relevance of increased angiogenesis in osteosarcoma.
abstract: OBJECTIVE
  The purpose of this work was to evaluate the prognostic relevance of microvessel density (MVD) for response to chemotherapy and long-term outcome in osteosarcoma.
  
  
  METHODS
  Pretherapeutic tumor biopsies of 60 patients with high-grade central osteosarcoma, who were treated according to multimodal neoadjuvant protocols of the German-Austrian-Swiss Cooperative Osteosarcoma Study Group, were evaluated for intratumoral MVD. MVD was correlated with demographic and tumor-related variables, response, and survival.
  
  
  RESULTS
  The median intratumoral MVD was 52 microvessels per 0.26-mm2 field area (interquartile range, 31-77 microvessels per 0.26-mm2 field area). At a median follow-up period of 3.5 years, patients with a high (>median) MVD had significantly higher 5- and 10-year overall survival rates (84%) than patients with low (< or =median) MVD (49%; P = 0.0029). Furthermore, increased relapse-free survival for patients with high MVD (P = 0.0064) was observed. In a subgroup analysis of 44 patients with primary high-grade central osteosarcoma of the extremities without primary metastases and good surgical remission, high MVD was associated with 5- and 10-year overall survival rates of 91% compared with 58% for low MVD (P = 0.034). Cox regression analysis revealed that MVD was an independent prognostic factor for survival. A good response to chemotherapy (histologic grading scale of Salzer-Kuntschik) correlated significantly with a high MVD (P = 0.006).
  
  
  CONCLUSIONS
  Increased angiogenesis is a prognostic indicator for higher survival and response rates to chemotherapy in patients with osteosarcoma. Thus, measurement of MVD might be useful in decisions selecting patients for future neoadjuvant treatment.
authors.affiliation: Department of Medicine/Hematology and Oncology, University Children's Hospital, University of Muenster, Muenster, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Kreuter
authors.forename: Ralf
authors.initials: R
authors.lastname: Bieker
authors.forename: Stefan S
authors.initials: SS
authors.lastname: Bielack
authors.forename: Tanja
authors.initials: T
authors.lastname: Auras
authors.forename: Horst
authors.initials: H
authors.lastname: Buerger
authors.forename: Georg
authors.initials: G
authors.lastname: Gosheger
authors.forename: Heribert
authors.initials: H
authors.lastname: Jurgens
authors.forename: Wolfgang E
authors.initials: WE
authors.lastname: Berdel
authors.forename: Rolf M
authors.initials: RM
authors.lastname: Mesters
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001859:Bone Neoplasms / Q000098:blood supply* / Q000473:pathology / Q000628:therapy; D002648:Child; D002675:Child, Preschool; D005121:Extremities; D005260:Female; D006801:Humans; D007867:Leg Bones; D008297:Male; D008833:Microcirculation; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D012516:Osteosarcoma / Q000098:blood supply* / Q000473:pathology / Q000628:therapy; D011379:Prognosis; D012189:Retrospective Studies; D015996:Survival Rate