Prognostic Significance of HIF-2alpha Expression on Tumor Infiltrating Macrophages in Patients with FIGO Stage IIIb Uterine Cervical Cancer undergoing Radiotherapy

Abstract

Purpose/Objective(s)Hypoxia-inducible factor (HIF)-2α, a basic helix-loop-helix (bHLH)-PAS protein is the principal regulator of the hypoxic transcriptional response. An immunohistochemical study reported strong HIF-2α expression in the cytoplasm of tumor infiltrative macrophages (TIMs). Previously, we assessed the expression of HIF-2α in human cervical cancer tissue before radiation therapy and reported the percentage of HIF-2α immunoreactivity in TIMs significantly correlated with only disease free survival (DFS). But previous survey we reported used the data collected from nonuniform clinical stages. So we re-surveyed the data of FIGO stage IIIb as mode vale.Materials/MethodsThirty-five patients with histologically proven primary advanced squamous cell carcinoma of FIGO stage IIIb uterine cervix underwent radiotherapy in Tokushima University Hospital after biopsy specimens were taken.ResultsAmong 35 specimens stained for HIF-2α, 27 (77.1%) exhibited HIF-2α immunoreactivity in the TIMs. In only 2 of 35 cases, HIF-2α immunoreactivity was observed in the nuclei of tumor cells. The HIF-2α positive cell count ratio in TIMs was associated with both DFS with the worst DFS (p = 0.043) and cause specific survival (CSS) with the worst CSS (p = 0.048) being in cases in the group with a high positive cell count ratio.ConclusionsThese findings might suggest that the ratio of the HIF-2α positive cell in TIMs may be a predictive indicator for prognosis before radiation therapy for stage IIIb uterine cervical cancer. Purpose/Objective(s)Hypoxia-inducible factor (HIF)-2α, a basic helix-loop-helix (bHLH)-PAS protein is the principal regulator of the hypoxic transcriptional response. An immunohistochemical study reported strong HIF-2α expression in the cytoplasm of tumor infiltrative macrophages (TIMs). Previously, we assessed the expression of HIF-2α in human cervical cancer tissue before radiation therapy and reported the percentage of HIF-2α immunoreactivity in TIMs significantly correlated with only disease free survival (DFS). But previous survey we reported used the data collected from nonuniform clinical stages. So we re-surveyed the data of FIGO stage IIIb as mode vale. Hypoxia-inducible factor (HIF)-2α, a basic helix-loop-helix (bHLH)-PAS protein is the principal regulator of the hypoxic transcriptional response. An immunohistochemical study reported strong HIF-2α expression in the cytoplasm of tumor infiltrative macrophages (TIMs). Previously, we assessed the expression of HIF-2α in human cervical cancer tissue before radiation therapy and reported the percentage of HIF-2α immunoreactivity in TIMs significantly correlated with only disease free survival (DFS). But previous survey we reported used the data collected from nonuniform clinical stages. So we re-surveyed the data of FIGO stage IIIb as mode vale. Materials/MethodsThirty-five patients with histologically proven primary advanced squamous cell carcinoma of FIGO stage IIIb uterine cervix underwent radiotherapy in Tokushima University Hospital after biopsy specimens were taken. Thirty-five patients with histologically proven primary advanced squamous cell carcinoma of FIGO stage IIIb uterine cervix underwent radiotherapy in Tokushima University Hospital after biopsy specimens were taken. ResultsAmong 35 specimens stained for HIF-2α, 27 (77.1%) exhibited HIF-2α immunoreactivity in the TIMs. In only 2 of 35 cases, HIF-2α immunoreactivity was observed in the nuclei of tumor cells. The HIF-2α positive cell count ratio in TIMs was associated with both DFS with the worst DFS (p = 0.043) and cause specific survival (CSS) with the worst CSS (p = 0.048) being in cases in the group with a high positive cell count ratio. Among 35 specimens stained for HIF-2α, 27 (77.1%) exhibited HIF-2α immunoreactivity in the TIMs. In only 2 of 35 cases, HIF-2α immunoreactivity was observed in the nuclei of tumor cells. The HIF-2α positive cell count ratio in TIMs was associated with both DFS with the worst DFS (p = 0.043) and cause specific survival (CSS) with the worst CSS (p = 0.048) being in cases in the group with a high positive cell count ratio. ConclusionsThese findings might suggest that the ratio of the HIF-2α positive cell in TIMs may be a predictive indicator for prognosis before radiation therapy for stage IIIb uterine cervical cancer. These findings might suggest that the ratio of the HIF-2α positive cell in TIMs may be a predictive indicator for prognosis before radiation therapy for stage IIIb uterine cervical cancer.