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The Korean Journal of Pathology 2005;39(5): 307-312.
Expression of Hypoxia Inducible Factor-1alpha in Invasive Squamous Cell Carcinoma of Uterine Cervix Treated by Radiotherapy.
Kyung Ja Lee, Min Sun Cho, Seung Cheol Kim, Hae Sung Moon, Hyesook Park, Shi Nae Lee, Sun Hee Sung, Ki Nam Shim, Kyung Eun Lee, Sung Ae Jung, Kwon Yoo, Hae Young Park, Soo Yeun Park, Eun Sun Yoo, Hyun Suk Suh
1Department of Radiation Oncology, Medical Research Center, College of Medicine, Ewha Womans University, Seoul, Korea.
2Department of Pathology, Medical Research Center, College of Medicine, Ewha Womans University, Seoul, Korea. mcho1124@ewha.ac.kr
3Department of Gynecology and Obstetrics, Medical Research Center, College of Medicine, Ewha Womans University, Seoul, Korea.
4Department of Preventive Medicine, Medical Research Center, College of Medicine, Ewha Womans University, Seoul, Korea.
5Department of Internal Medicine, Medical Research Center, College of Medicine, Ewha Womans University, Seoul, Korea.
6Department of Biochemistry, Medical Research Center, College of Medicine, Ewha Womans University, Seoul, Korea.
7Department of Anatomy, Medical Research Center, College of Medicine, Ewha Womans University, Seoul, Korea.
8Department of Pediatrics, Medical Research Center, College of Medicine, Ewha Womans University, Seoul, Korea.
ABSTRACT
BACKGROUND: Hypoxia-inducible factor-1alpha (HIF-1alpha) is an intrinsic marker of tumor hypoxia, and this is associated with reduced radiosensitivity. Furthermore, HIF-1alpha can increase a tumor's aggressiveness by promoting neoangiogenesis, cell proliferation and survival, and invasion. METHODS: The expression of HIF-1alpha was was investigated by performing immunohistochemistry on the cervical tissue specimens obtained from 57 patients who had received radiotherapy combined with or without chemotherapy for stages I-III cervical squamous cell carcinoma. The staining results were compared with anemia, the stage, the radiotherapy response and patient survival by univariate and multivariate analysis. RESULTS: In 57 patients, the expression of HIF-1alpha was seen in the tissue specimens of 46 patients (81.7%). Among them, 25 (54.3%), 14 (30.4%), and 7 (15.2%) of the patients' tissue specimens showed weak, moderate and strong expressions, respectively. Six patients had a partial response after radiotherapy. Twelve patients (21.1%) died of cervical cancer. The increased expression of HIF-1alpha was significantly associated (p<0.05) with the disease stage and anemia. There were significant positive correlations between the increased expression of HIF-1alpha and the poor response after radiotherapy and the patients' survival. CONCLUSIONS: The present result suggests that the overexpression of HIF-1alpha in the uterine cervix could be used as a prognostic indicator for the patients treated with radiotherapy.
Key Words: Cervix Neoplasms; Carcinoma, Squamous cell; Hypoxia Inducible Factor 1; Immunohistochemistry