Hypoxia markers in human osteosarcoma: an exploratory study.
Neoplastic cells growing under hypoxic conditions exhibit a more aggressive phenotype by activating a cascade of molecular events partly mediated by hypoxia-inducible transcription factor (HIF-1alpha) and vascular endothelial growth factor (VEGF). The roles of these markers have been studied previously in several cancer lines. We ascertained the frequency of HIF-1alpha expression, VEGF expression, the degree of neovascularization, and cell proliferation in osteosarcoma samples. Samples from osteosarcoma patients were assessed for HIF-1alpha and VEGF protein expression using immunohistochemistry, neovascularization using antibodies for Factor VIII, and cell proliferation using the Ki-67 labeling index. Associations between these parameters and clinical features were examined. HIF-1alpha staining was positive in 35% of patients and metastases were present in 61% of these HIF-1alpha-positive patients. VEGF protein expression was detected in 69% of patients, 92% of whom were female. We observed an insignificant trend for a higher frequency of VEGF expression in the high-grade as compared to low-grade osteosarcoma. We observed no association between vascular density and proliferation index and any clinical parameters. We found an association between HIF-1alpha expression and metastatic disease and between VEGF expression and female gender.
Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
Hiroo
H
Mizobuchi
José Manuel
JM
García-Castellano
Shaji
S
Philip
John H
JH
Healey
Richard
R
Gorlick
D000293:Adolescent; D000328:Adult; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001859:Bone Neoplasms / Q000378:metabolism* / Q000473:pathology; D049109:Cell Proliferation; D002648:Child; D005260:Female; D005266:Femoral Neoplasms / Q000378:metabolism / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D000860:Hypoxia / Q000378:metabolism; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D012516:Osteosarcoma / Q000378:metabolism* / Q000473:pathology; D012737:Sex Factors; D013977:Tibia; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
D014408:Biomarkers, Tumor; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D019394:Ki-67 Antigen; D042461:Vascular Endothelial Growth Factor A