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.
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
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.