Kubo T, Sugita T, Shimose S, Matsuo T, Arihiro K, Ochi M
Department of Orthopaedic Surgery, Hiroshima University, Hiroshima, Japan.
J Bone Joint Surg Br. 2008 Mar;90(3):364-70. doi: 10.1302/0301-620X.90B3.19806.
We investigated the use of hypoxia-inducible factor (HIF) proteins as prognostic markers in chondrosarcoma and the relationship of HIF to the biological characteristics of cartilage tumours. The expression of HIF-1alpha, HIF-2alpha, proliferating cell nuclear antigen (PCNA) and microvessel density (MVD) were measured immunohistochemically in 29 specimens of cartilage tumour. There was no HIF-1alpha and HIF-2alpha staining in any of the nine benign cartilage tumours. In 20 specimens of chondrosarcoma, the rate of HIF-1alpha and HIF-2alpha expression was 40% and 25%, respectively. The tumour size (> or = 8 cm), histological grade (grade 2 and grade 3) surgical margin (marginal and intralesional) and HIF-1alpha expression (positive) correlated significantly with a shorter disease-free survival. There was a significant association between HIF-1alpha and the MVD and a strong trend towards a correlation between HIF-1alpha and the PCNA index or histological grade. Our findings suggest that HIF-1alpha protein may be a useful objective marker in the assessment of the prognosis in chondrosarcoma, since it plays an important role in tumour angiogenesis and cell proliferation.
我们研究了缺氧诱导因子(HIF)蛋白作为软骨肉瘤预后标志物的应用以及HIF与软骨肿瘤生物学特性的关系。采用免疫组织化学方法检测了29例软骨肿瘤标本中HIF-1α、HIF-2α、增殖细胞核抗原(PCNA)和微血管密度(MVD)的表达。9例良性软骨肿瘤中均未检测到HIF-1α和HIF-2α染色。在20例软骨肉瘤标本中,HIF-1α和HIF-2α的表达率分别为40%和25%。肿瘤大小(≥8 cm)、组织学分级(2级和3级)、手术切缘(边缘和瘤内)以及HIF-1α表达(阳性)与无病生存期缩短显著相关。HIF-1α与MVD之间存在显著关联,且HIF-1α与PCNA指数或组织学分级之间有很强的相关性趋势。我们的研究结果表明,HIF-1α蛋白可能是评估软骨肉瘤预后的有用客观标志物,因为它在肿瘤血管生成和细胞增殖中起重要作用。