PURPOSE: The purpose is to investigate the impact of hypoxia-inducible factor (HIF)-1alpha expression on response to radiotherapy and prognosis of patients with primary irradiated cervical cancer. Because human papillomavirus (HPV) oncoprotein E6 might interact with HIF-1alpha in various pathways, we also investigated the relation of HIF-1alpha and HPV status. EXPERIMENTAL DESIGN: Expression of HIF-1alpha was investigated by immunohistochemistry in 67 specimens of patients who had received radical radiotherapy for cervical cancer stages IB-IIIB. HPV analysis was performed using type-specific PCR, cloning, and sequencing. Survival analysis was performed using univariate and multivariate analysis. RESULTS: Immunohistochemistry revealed expression of HIF-1alpha in 72.1% of the tumor samples. In 16 (23.9%) cases, there was a weak expression, in 25 (37.3%) a moderate expression, and in 7 cases (10.4%) a strong expression of HIF-1alpha. Nineteen samples (28.4%) were considered negative for HIF-1alpha expression. Strong/moderate expression of HIF-1alpha was associated with only partial response to radiotherapy (P = 0.037, chi(2) test). Strong/moderate expression of HIF-1alpha was also an independent prognostic factor for shorter progression-free survival (P = 0.036, Cox regression) and cervical cancer-specific survival (P = 0.04, Cox regression). No association between HIF-1alpha expression and infection with different HPV types could be found. CONCLUSIONS: Overexpression of HIF-1alpha has predictive and prognostic significance in cervical cancer patients receiving curative radiation therapy. Possibly, expression of HIF-1alpha could serve as intrinsic marker of hypoxia in cervical cancer.
PURPOSE: The purpose is to investigate the impact of hypoxia-inducible factor (HIF)-1alpha expression on response to radiotherapy and prognosis of patients with primary irradiated cervical cancer. Because human papillomavirus (HPV) oncoprotein E6 might interact with HIF-1alpha in various pathways, we also investigated the relation of HIF-1alpha and HPV status. EXPERIMENTAL DESIGN: Expression of HIF-1alpha was investigated by immunohistochemistry in 67 specimens of patients who had received radical radiotherapy for cervical cancer stages IB-IIIB. HPV analysis was performed using type-specific PCR, cloning, and sequencing. Survival analysis was performed using univariate and multivariate analysis. RESULTS: Immunohistochemistry revealed expression of HIF-1alpha in 72.1% of the tumor samples. In 16 (23.9%) cases, there was a weak expression, in 25 (37.3%) a moderate expression, and in 7 cases (10.4%) a strong expression of HIF-1alpha. Nineteen samples (28.4%) were considered negative for HIF-1alpha expression. Strong/moderate expression of HIF-1alpha was associated with only partial response to radiotherapy (P = 0.037, chi(2) test). Strong/moderate expression of HIF-1alpha was also an independent prognostic factor for shorter progression-free survival (P = 0.036, Cox regression) and cervical cancer-specific survival (P = 0.04, Cox regression). No association between HIF-1alpha expression and infection with different HPV types could be found. CONCLUSIONS: Overexpression of HIF-1alpha has predictive and prognostic significance in cervical cancerpatients receiving curative radiation therapy. Possibly, expression of HIF-1alpha could serve as intrinsic marker of hypoxia in cervical cancer.
Authors: Jing Zeng; Alfred P See; Khaled Aziz; Saravanan Thiyagarajan; Tarek Salih; Rajendra P Gajula; Michael Armour; Jillian Phallen; Stephanie Terezakis; Lawrence Kleinberg; Kristen Redmond; Russell K Hales; Roberto Salvatori; Alfredo Quinones-Hinojosa; Phuoc T Tran; Michael Lim Journal: Cancer Biol Ther Date: 2011-10-01 Impact factor: 4.742
Authors: A S Berghoff; A Ilhan-Mutlu; A Wöhrer; M Hackl; G Widhalm; J A Hainfellner; K Dieckmann; T Melchardt; B Dome; H Heinzl; P Birner; M Preusser Journal: Strahlenther Onkol Date: 2014-02-28 Impact factor: 3.621