Hypoxia-inducible factor 1 alpha in high-risk breast cancer: an independent prognostic parameter?

被引:116
作者
Gruber, G
Greiner, RH
Hlushchuk, R
Aebersold, DM
Altermatt, HJ
Berclaz, G
Djonov, V
机构
[1] Univ Bern, Inst Anat, CH-3012 Bern, Switzerland
[2] Univ Bern, Dept Gynaecol, CH-3012 Bern, Switzerland
[3] Univ Bern, Dept Radiat Oncol, CH-3012 Bern, Switzerland
来源
BREAST CANCER RESEARCH | 2004年 / 6卷 / 03期
关键词
breast cancer; hypoxia-inducible factor 1 alpha; prognostic marker; tumor hypoxia;
D O I
10.1186/bcr775
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background: Hypoxia-inducible factor 1 alpha (hif-1alpha) furnishes tumor cells with the means of adapting to stress parameters like tumor hypoxia and promotes critical steps in tumor progression and aggressiveness. We investigated the role of hif-1alpha expression in patients with node-positive breast cancer. Methods: Tumor samples from 77 patients were available for immunohistochemistry. The impact of hif-1alpha immunoreactivity on survival endpoints was determined by univariate and multivariate analyses, and correlations to clinicopathological characteristics were determined by cross-tabulations. Results: hif-1alpha was expressed in 56% (n = 43/77) of the patients. Its expression correlated with progesterone receptor negativity ( P = 0.002). The Kaplan-Meier curves revealed significantly shorter distant metastasis-free survival (DMFS) (P = 0.04, log-rank) and disease-free survival (DFS) (P = 0.04, log-rank) in patients with increased hif-1alpha expression. The difference in overall survival (OS) did not attain statistical significance (5-year OS, 66% without hif-1alpha expression and 55% with hif-1alpha expression; P = 0.21). The multivariate analysis failed to reveal an independent prognostic value for hif-1alpha expression in the whole patient group. The only significant parameter for all endpoints was the T stage (T3/T4 versus T1/T2: DMFS, relative risk = 3.16, P = 0.01; DFS, relative risk = 2.57, P = 0.03; OS, relative risk = 3.03, P = 0.03). Restricting the univariate and multivariate analyses to T1/T2 tumors, hif-1alpha expression was a significant parameter for DFS and DMFS. Conclusions: hif-1alpha is expressed in the majority of patients with node-positive breast cancer. It can serve as a prognostic marker for an unfavorable outcome in those with T1/T2 tumors and positive axillary lymph nodes.
引用
收藏
页码:R191 / R198
页数:8
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