Expression of hypoxia-inducible factor-1
in esophageal squamous cell carcinoma
Authors: Matsuyama, Tomokazu; Nakanishi, Kuniaki1; Hayashi, Takuya2; Yoshizumi, Yutaka3; Aiko, Satoshi3; Sugiura, Yoshiaki3; Tanimoto, Takao4; Uenoyama, Maki2; Ozeki, Yuichi3; Maehara, Tadaaki3
Source: Cancer Science, Volume 96, Number 3, March 2005 , pp. 176-182(7)
Publisher: Blackwell Publishing
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Abstract:
Hypoxia-inducible factor-1 (HIF-1) is a transcription factor that plays an important role in tumor growth and metastasis by regulating energy metabolism and inducing angiogenesis. Elevated levels of HIF-1, a subunit of HIF-1, are noted in various malignant tumors, but it is unclear whether this is so in esophageal carcinoma. The purpose of this study was to evaluate the implications of HIF-1 expression in esophageal squamous cell carcinoma. In 215 patients with esophageal carcinoma, we examined immunoreactivity for HIF-1 protein, vascular endothelial growth factor (VEGF) protein and p53 protein. In 38 patients, we examined the expression of HIF-1 messenger ribonucleic acid (mRNA) (using the semiquantitative reverse transcriptase-polymerase chain reaction [RT-PCR]). A positive HIF-1 protein expression was recognized in 95% of the patients, and was strongly apparent within both the nuclei and/or cytoplasm of tumor cells. The proportion of patients in the ‘high score’ group for HIF-1 protein expression increased significantly with increasing VEGF protein expression. Immunoreactivity for HIF-1 protein was found to have a significant effect on disease-free survival rate in our univariate analysis, but no effect on overall survival rate. In RT-PCR, HIF-1 mRNA scores correlated significantly with scores for HIF-1 protein expression, but not with any clinicopathologic factor or either of the survival rates. The detection of HIF-1 protein and mRNA would appear to offer limited information as to progression and prognosis in esophageal carcinoma. (Cancer Sci 2005; 96: 176–182)
Document Type: Research article
DOI: 10.1111/j.1349-7006.2005.00025.x
Affiliations: 1: First Department of Pathology, 2: Division of Environmental Medicine and 3: Surgery II, 4: Second Department of Pathology, National Defense Medical College, Tokorozawa, Japan
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