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Prognostic significance of Hypoxia-Inducible Factor 1 alpha(HIF-1alpha) expression in serous ovarian cancer: an immunohistochemical study
dc.creator | Daponte, A. | en |
dc.creator | Ioannou, M. | en |
dc.creator | Mylonis, I. | en |
dc.creator | Simos, G. | en |
dc.creator | Minas, M. | en |
dc.creator | Messinis, I. E. | en |
dc.creator | Koukoulis, G. | en |
dc.date.accessioned | 2015-11-23T10:25:08Z | |
dc.date.available | 2015-11-23T10:25:08Z | |
dc.date.issued | 2008 | |
dc.identifier | 10.1186/1471-2407-8-335 | |
dc.identifier.issn | 1471-2407 | |
dc.identifier.uri | http://hdl.handle.net/11615/26897 | |
dc.description.abstract | Background: The hypoxia-inducible factor (HIF) has emerged as an attractive target for cancer therapy. The few publications addressing the prognostic significance of Hypoxia-Inducible Factor 1 alpha (HIF-1 alpha) cellular expression in ovarian cancer produced contradictory findings which are not permissible to widely acceptable conclusions and clinical applications. Our study was designed to investigate this by including a comparatively large number of cases and by using a combination of antibodies to analyze immunohistochemically the expression of HIF-1 alpha. Methods: One hundred (n = 100) neoplastic and 20 benign (controls) pathological samples from paraffin-embedded tissue were included. They were classified after surgery as stage I (n = 23) and stage III G3 (n = 55). Also 22 borderline serous adenocarcinoma patients and 20 benign controls were stained. The mean follow up was 3 years. Only patients with the diagnosis of serous carcinoma of stage III, G3 who received 6 cycles of postoperative TC (175-180 mg/m2 paclitaxel and carboplatin after calculating the area under the concentration curve) with complete medical records (n = 55) were selected for survival analysis. The survival analysis of the samples compared two groups after the patients were dichotomized by HIF-1 alpha final score to positive and negative. Results: The frequency of the nuclear expression of HIF-1 alpha in benign tumours was significantly lower (median: no expression) than in borderline and ovarian cancer tumours combined (p < 0.001). HIF-1 alpha expression in serous ovarian carcinoma was not stage dependent. The overall survival of patients with tumours that stained strongly for HIF-1 alpha was significantly shorter than that of patients with tumours that stained weakly or were negative for HIF-1 alpha (p = 0.01). Kaplan-Meier survival curves confirmed that HIF-1 alpha "positive" had decreased overall survival compared to HIF-1 alpha "negative" patients (p = 0.003) and this was an independent adverse prognostic factor (multivariable analysis p = 0.006). HIF-1 alpha "positive" patients displayed a shorter median progress free interval (PFI) (not statistically significant p > 0.05). Interestingly the overall PFI of the subgroup of patients that have undergone suboptimal cytoreduction at primary surgery (n = 21) with tumours that stained strongly for HIF-1 alpha was significantly worse than that of patients with tumours that stained weakly or were negative for HIF-1 alpha (p = 0.03). Conclusion: Our report confirms the prognostic value of HIF-1 alpha when restricted to poorly differentiated serous ovarian carcinoma. In addition it shows that this association is elusive, since it is not only methodology-related but it can be antibody-depended. There is adequate evidence to speculate that targeting HIF-1 alpha could improve the long-term prognosis of these patients In order to increase the overall sensitivity of the immunoassay, maintaining acceptable levels of specificity, a panel of antibodies should be used. | en |
dc.source.uri | <Go to ISI>://WOS:000264053100001 | |
dc.subject | FACTORS HIF-1-ALPHA | en |
dc.subject | FACTOR 1-ALPHA | en |
dc.subject | TUMOR-GROWTH | en |
dc.subject | NECK-CANCER | en |
dc.subject | THERAPY | en |
dc.subject | HYPOXIA-INDUCIBLE-FACTOR-1-ALPHA | en |
dc.subject | ANGIOGENESIS | en |
dc.subject | CARCINOMA | en |
dc.subject | GENE | en |
dc.subject | HEAD | en |
dc.subject | Oncology | en |
dc.title | Prognostic significance of Hypoxia-Inducible Factor 1 alpha(HIF-1alpha) expression in serous ovarian cancer: an immunohistochemical study | en |
dc.type | journalArticle | en |
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