Fillies Thomas, Werkmeister Richard, van Diest Paul J, Brandt Burkhard, Joos Ulrich, Buerger Horst
Department of Cranio-Maxillofacial Surgery, University of Münster, Waldeyerstrasse 30, 48129 Münster, Germany.
BMC Cancer. 2005 Jul 21;5:84. doi: 10.1186/1471-2407-5-84.
Hypoxia-inducible factor 1 (HIF-1) is a transcription factor, which plays a central role in biologic processes under hypoxic conditions, especially concerning tumour angiogenesis. HIF-1alpha is the relevant, oxygen-dependent subunit and its overexpression has been associated with a poor prognosis in a variety of malignant tumours. Therefore, HIF-1alpha expression in early stage oral carcinomas was evaluated in relation to established clinico-pathological features in order to determine its value as a prognostic marker.
85 patients with histologically proven surgically treated T1/2 squamous cell carcinoma (SCC) of the oral floor were eligible for the study. Tumor specimens were investigated by means of tissue micro arrays (TMAs) and immunohistochemistry for the expression of HIF-1. Correlations between clinical features and the expression of HIF-1 were evaluated by Kaplan-Meier curves, log-rank tests and multivariate Cox regression analysis.
HIF-1alpha was frequently overexpressed in a probably non-hypoxia related fashion. The expression of HIF-1alpha was related with a significantly improved 5-year survival rate (p < 0.01) and a significantly increased disease free period (p = 0.01) independent from nodal status and tumour size. In primary node negative T1/T2 SCC of the oral floor, absence of HIF-1alpha expression specified a subgroup of high-risk patients (p < 0.05).
HIF-1alpha overexpression is an indicator of favourable prognosis in T1 and T2 SCC of the oral floor. Node negative patients lacking HIF-1alpha expression may therefore be considered for adjuvant radiotherapy.
缺氧诱导因子1（HIF-1）是一种转录因子，在缺氧条件下的生物过程中起核心作用，尤其与肿瘤血管生成有关。HIF-1α是相关的氧依赖性亚基，其过表达与多种恶性肿瘤的不良预后相关。因此，评估早期口腔癌中HIF-1α的表达与既定临床病理特征的关系，以确定其作为预后标志物的价值。
85例经组织学证实接受手术治疗的口腔底T1/2鳞状细胞癌（SCC）患者符合本研究条件。通过组织微阵列（TMA）和免疫组织化学研究肿瘤标本中HIF-1的表达。通过Kaplan-Meier曲线、对数秩检验和多变量Cox回归分析评估临床特征与HIF-1表达之间的相关性。
HIF-1α经常以可能与缺氧无关的方式过表达。HIF-1α的表达与5年生存率显著提高（p < 0.01）和无病生存期显著延长（p = 0.01）相关，且与淋巴结状态和肿瘤大小无关。在口腔底原发性淋巴结阴性的T1/T2 SCC中，HIF-1α表达缺失确定了一组高危患者（p < 0.05）。
HIF-1α过表达是口腔底T1和T2 SCC预后良好的指标。因此，对于缺乏HIF-1α表达的淋巴结阴性患者，可考虑辅助放疗。
