Ishikawa Hitoshi, Sakurai Hideyuki, Hasegawa Masatoshi, Mitsuhashi Norio, Takahashi Mitsuhiro, Masuda Norihiro, Nakajima Masanobu, Kitamoto Yoshizumi, Saitoh Jun-Ichi, Nakano Takashi
Department of Radiation Oncology, Gunma University Graduate School of Medicine, Gunma, Japan.
Int J Radiat Oncol Biol Phys. 2004 Oct 1;60(2):513-21. doi: 10.1016/j.ijrobp.2004.03.025.
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.
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.
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.
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.
缺氧诱导因子-1α（HIF-1α）是肿瘤缺氧的内在标志物。一般认为缺氧状态会降低放射敏感性，但HIF-1α在晚期宫颈癌中的作用仍不清楚。本研究的目的是阐明HIF-1α、人乳头瘤病毒（HPV）以及其他分子因素，如p53、bax、bcl-2及其相关性对IIIB期宫颈癌患者放射治疗结局的影响。
我们分析了38例仅接受放射治疗的国际妇产科联盟（FIGO）IIIB期宫颈鳞状细胞癌患者。所有患者均接受外照射和低剂量率腔内近距离放射治疗联合治疗。通过对治疗前石蜡包埋标本进行免疫组织化学染色来检测肿瘤中HIF-1α、p53、bax和bcl-2的表达。还通过聚合酶链反应检测HPV感染情况。通过单因素分析来分析这些参数对临床结局的影响。
38例患者中，HIF-1α、p53、bax和bcl-2高表达的患者分别有17例（45%）、22例（58%）、15例（39%）和15例（39%），28例患者（74%）HPV感染呈阳性。HIF-1α高表达与疾病复发之间存在显著正相关（p < 0.05）。此外，HIF-1α与无复发生存率有显著相关性（p = 0.04）。HIF-1α高表达与局部控制率之间未发现统计学相关性（p = 0.17），而HIF-1α状态对远处转移具有很强的预测意义（p = 0.03）。相反，其他因素对临床结局无影响。
目前的结果表明，HIF-1α是一个重要的预后因素，特别是对于预测IIIB期宫颈鳞状细胞癌患者放射治疗后的未来转移情况。
