Department of Gynaecological Oncology, University Medical Centre Utrecht, The Netherlands.
BMC Cancer. 2010 Jun 19;10:307. doi: 10.1186/1471-2407-10-307.
Hypoxia inducible factor 1alpha (HIF-1alpha) plays an essential role in the adaptive response of cells to hypoxia and is associated with aggressive tumour behaviour. We have shown p27kip1, which is generally reduced in endometrial cancer, to be re-expressed in hypoxic regions. This possibly contributes to survival of cancer cells. The aim of this study was to evaluate the prognostic value of HIF-1alpha and p27kip expression in patients with endometrioid endometrial cancer.
Expression levels of HIF-1alpha, CAIX, Glut-1, and p27kip1 were analyzed by immunohistochemistry. Percentage of positive cells, staining pattern (perinecrotic, diffuse, or mixed) and presence of necrosis were noted.
Necrosis was correlated with shortened disease free survival (DFS) (p = 0.008) and overall survival (OS) (p = 0.045). For DFS, perinecrotic HIF-1alpha expression was also prognostic (p = 0.044). Moreover, high p27kip1 expression was an additional prognostic factor for these patients with perinecrotic HIF-1alpha expression. In multivariate Cox regression, perinecrotic HIF-expression emerged as an independent prognostic factor. Perinecrotic HIF-1alpha expression was significantly associated with CAIX and Glut-1 expression, pointing towards functional HIF-1.
In patients with endometrioid endometrial cancer, necrosis and necrosis-related expression of HIF-1alpha are important prognostic factors. More aggressive adjuvant treatment might be necessary to improve the outcome of patients with these characteristics.
缺氧诱导因子 1alpha（HIF-1alpha）在细胞对缺氧的适应反应中起着至关重要的作用，并且与侵袭性肿瘤行为相关。我们已经表明，p27kip1 在子宫内膜癌中通常减少，在缺氧区域重新表达。这可能有助于癌细胞的存活。本研究的目的是评估缺氧诱导因子 1alpha（HIF-1alpha）和 p27kip1 在子宫内膜样子宫内膜癌患者中的预后价值。
通过免疫组织化学分析 HIF-1alpha、CAIX、Glut-1 和 p27kip1 的表达水平。记录阳性细胞的百分比、染色模式（坏死周围、弥漫或混合）和坏死的存在。
坏死与无病生存期（DFS）（p = 0.008）和总生存期（OS）（p = 0.045）缩短相关。对于 DFS，坏死周围的 HIF-1alpha 表达也是预后因素（p = 0.044）。此外，高 p27kip1 表达是这些具有坏死周围 HIF-1alpha 表达的患者的另一个预后因素。在多变量 Cox 回归中，坏死周围的 HIF 表达是一个独立的预后因素。坏死周围的 HIF-1alpha 表达与 CAIX 和 Glut-1 表达显著相关，表明 HIF-1 具有功能。
在子宫内膜样子宫内膜癌患者中，坏死和与坏死相关的 HIF-1alpha 表达是重要的预后因素。可能需要更积极的辅助治疗，以改善具有这些特征的患者的预后。
