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The Korean Journal of Pathology 2009;43(1): 13-19.
doi: https://doi.org/10.4132/KoreanJPathol.2009.43.1.13
The Expression of Hypoxia Inducible Factor-1alpha and Its Correlation with the Expressions of Cyclin A1 and Cyclin B1 and the Clinicopathologic Factors of Uterine Cervical Carcinoma.
Ju Yeon Pyo, Jae Ho Cho, Hyunki Kim, Jong Pil Park, Young Tae Kim, Nam Hoon Cho
1Department of Pathology, College of Medicine, Yonsei University, Korea. cho1988@yuhs.ac
2Department of Radiation Oncology, College of Medicine, Yonsei University, Korea.
3Department of Obstetrics and Gynecology, College of Medicine, Yonsei University, Korea.
4Brain Korea 21 Project for Medical Science, Seoul, Korea.
ABSTRACT
BACKGROUND: Hypoxia inducible factor-1alpha(HIF-1alpha) is a transcription factor for various target genes that are involved in adapting cells to hypoxia. It promotes cell proliferation and survival via modulation of such cell cycle regulators such as cyclin A1 and cyclin B1 in response to hypoxia. This is associated with local failure of radiotherapy, which renders a poor prognosis for cervical carcinoma. METHODS: Using the tissue histologic sections and a tissue microarray of the archived biopsy and surgical specimens of uterine cervical carcinoma from 57 patients who were treated with radiation therapy alone, we performed immunohistochemical staining for HIF-1alpha and cyclin A1 and B1 to evaluate the correlations between the expressions of these proteins in tumors and the clinicopathologic parameters associated with the prognosis. RESULTS: The large tumor cell nests and invasive front margins of the tumors showed comparatively intense immunoreactivity of HIF-1alpha. There was no significant correlation between the HIF-1alpha, cyclin A1 and cyclin B1 expressions and the clinicopathologic factors. CONCLUSIONS: The HIF-1alpha expression showed marked intra-tumoral heterogeneity. The HIF-1alpha expression is neither a powerful predictor of resistance to radiotherapy nor is it a poor prognostic marker in cervical carcinoma patients who are treated with radiotherapy. The expressions of cyclin A1 and cyclin B1 are neither independently associated with the response of radiation therapy nor are they associated with the prognostic parameters of uterine cervical carcinoma.
Key Words: Cervix cancer; Radiotherapy; Hypoxia inducible factor 1, alpha subunit; Cyclin A; Cyclin B