Prognostic relevance of increased angiogenesis in osteosarcoma.
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.
Kreuter
Michael
M
Department of Medicine/Hematology and Oncology, University Children's Hospital, University of Muenster, Muenster, Germany.
Bieker
Ralf
R
Bielack
Stefan S
SS
Auras
Tanja
T
Buerger
Horst
H
Gosheger
Georg
G
Jurgens
Heribert
H
Berdel
Wolfgang E
WE
Mesters
Rolf M
RM
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