Overexpression of hypoxia-inducible-factor 1alpha(HIF-1alpha) in oesophageal squamous cell carcinoma correlates with lymph node metastasis and pathologic stage

Abstract

The purpose of this study is to investigate the clinical and histopathologic significance of hypoxia-inducible-factor 1alpha (HIF-1alpha) expression in oesophageal squamous cell carcinoma. One hundred and thirty surgically resected specimens of OSCC were immunohistochemically assessed for HIF-1alpha expression with monoclonal antibody. High HIF-1alpha immunostaining was detected in 40 specimens. The percentage of high HIF-1alpha expression cases increased with tumour stage according to pTNM system. High HIF-1alpha expression correlated with pTNM stage, depth of tumour invasion, lymph node metastasis, distant metastasis, lymphatic invasion and positive surgical margin. The overall survival rate was worse in patients with high HIF-1alpha pattern than in patients with low-expression pattern. Univariate analyses identified high HIF-1alpha positivity, depth of tumour invasion, lymph node metastasis, distant metastasis, lymphatic invasion, and a positive surgical margin as risk factors. Multivariate analyses indicated that depth of tumour invasion, lymph node metastasis and positive surgical margin, but not HIF-1alpha, were independent prognostic factors. Survival in patients with a high HIF-1alpha expression was significantly worse than in those with low expression in patient treated with adjuvant therapy.

Figure 1

Representative photomicrographs of immunohistochemical staining of HIF1α (× 200). Tumour cell immunoreactivity was scored based on nuclear and cytoplasmic staining. (A) −, no staining (B) 1+, nuclear staining in less than 1% of cells (C) nuclear staining in 1-10% of cells and/or with weak cytoplasmic staining (D) 3+, nuclear staining in 10-50% of cells and/or with distinct cytoplasmic staining, (E) 4+, nuclear staining in more than 50% of cells and/or with strong cytoplasmic staining. (F) HIF-1α-positive cells are already found in carcinoma in situ.

Figure 2

Kaplan–Meier overall survival curves of patients with OSCC with and without high HIF-1α expression. P=0.0007 by the log-rank test.

Figure 3

Kaplan–Meier overall survival curves of patients with OSCC underwent adjuvant therapy with or without high HIF-1α expression. P=0.0464 by the log-rank test.