Expression of hypoxic-inducible factor lα predicts metastasis-free survival after radiation therapy alone in stage IIIB cervical squamous cell carcinoma
Expression of hypoxic-inducible factor lα predicts metastasis-free survival after radiation therapy alone in stage IIIB cervical squamous cell carcinoma
复制标题
DOI：
10.1016/j.ijrobp.2004.03.025
复制
发表时间：
2004-10-01
影响因子：
7
通讯作者：
Nakano, T
中科院分区：
文献类型：
--
作者：
Ishikawa, H;Sakurai, H;Nakano, T
目的：缺氧诱导因子-1 α（HIF-1 α）是肿瘤缺氧的内在标志物。目前认为低氧状态降低了放射敏感性，但HIF-1 α在晚期宫颈癌中的作用尚不清楚。本研究的目的是澄清HIF-1 α，人乳头瘤病毒（HPV），和其他分子因素，如p53，bax，bcl-2，和它们的相关性对患者的结果与第IIIB期宫颈癌在放射治疗。方法和材料：我们分析了38例FIGO第IIIB期宫颈鳞状细胞癌与放射治疗单独治疗。所有患者均接受外照射和低剂量率腔内后装治疗的联合治疗。采用免疫组化法检测HIF-1 α、p53、bax、bcl-2蛋白的表达。聚合酶链反应检测HPV感染。结果：38例宫颈癌中HIF-1 α、p53、bax和bcl-2蛋白高表达分别为45%（17/38）、58%（22/38）、39%（15/38）和39%（15/38），HPV阳性24%（28/78）。HIF-1 α高表达与肿瘤复发呈正相关（p < 0.05）。此外，HIF-1 α与无复发生存率显著相关（p = 0.04）。HIF-1 α高表达与局部控制率之间无统计学相关性（p = 0.17），而HIF-1 α状态预测远处转移具有显著性（p = 0.03）。相反，其他因素没有表现出对临床outcome.Conclusions的影响：目前的研究结果表明，HIF-1 α是一个重要的预后因素，特别是对预测未来的转移放射治疗后的第IIIB期宫颈鳞状细胞癌患者。(C)2004年爱思唯尔公司
Purpose: Hypoxia-inducible factor-1alpha (HIF-1alpha) is an intrinsic marker of tumor hypoxia. It has been considered that the hypoxic status reduces radiosensitivity, but the role of HIF-1alpha in advanced cervical carcinoma is still unclear. The objective of this study was to clarify the impact of HIF-1alpha, human papillomavirus (HPV), and other molecular factors, such as p53, bax, bcl-2, and their correlations on the outcome of patients with Stage IIIB cervical carcinoma in radiation therapy.Methods and Materials: We analyzed 38 patients with FIGO Stage IIIB squamous cell carcinoma of the cervix treated with radiation therapy alone. All patients received the combination therapy of external beam irradiation and low-dose-rate intracavity brachytherapy. The tumor expressions of HIF-1alpha, p53, bax, and bcl-2 were examined by immunohistochemical staining of the pretreatment paraffin embedded specimens. HPV infection was also detected by polymerase chain reaction. The effects of these parameters on clinical outcomes were analyzed by univariate analysis.Results: Of 38 patients, high expression of HIF-1alpha, p53, bax, and bcl-2 were seen in 17 (45%), 22 (58%), 15 (39%), and 15 (39%) patients, respectively, and 28 patients (74%) showed positive infection with HPV. There was a significant positive correlation between high HIF-1alpha expression and disease recurrence (p < 0.05). Furthermore, HIF-1alpha had a significant correlation with the recurrence-free survival rate (p = 0.04). No statistical correlation was noted between high HIF-1alpha expression and the local control rate (p = 0.17), whereas the HIF-1alpha status predicted distant metastasis with strong significance (p = 0.03). Conversely, other factors demonstrated no impact on the clinical outcome.Conclusions: The present results suggest that HIF-1alpha is an important prognostic factor, especially for predicting future metastasis after radiation therapy for patients with Stage IIIB squamous cell carcinoma of the cervix. (C) 2004 Elsevier Inc.