Overexpression of HIF-1 alpha indicates a poor prognosis in tongue carcinoma and may be associated with tumour metastasis

摘要

Expression of the transcription factor hypoxia-inducible factor 1 (HIF-1) plays a key role in cellular adaptation to hypoxia, particularly in relation to tumour angiogenesis. Expression of the HIF-1 alpha subunit is responsive to changes in oxygen levels. Overexpression of HIF-1 alpha has been reported to be associated with a poor prognosis in a variety of malignant tumours. The objective of this study was to investigate whether the expression of HIF-1 alpha in tongue carcinoma was associated with established clinicopathological features. Tumour specimens from 120 patients with histologically-proven, surgically-treated tongue carcinoma were examined by immunohistochemical staining for expression of HIF-1 alpha. The mRNA levels of HIF-1 alpha were measured in 45 fresh, paired samples of tongue carcinoma and corresponding adjacent normal tissues using quantitative RT-PCR (qRT-PCR). HIF-1 alpha was found to be frequently overexpressed in tumours in a hypoxia-independent manner. The expression of HIF-1 alpha correlated with the five-year survival rate (P<0.01) and disease-free period (P<0.01). Increased expression of HIF-1 alpha correlated significantly with clinical stage (P=0.002) and lymph node metastasis (P=0.034). Compared with paired normal tissues, HIF-1 alpha mRNA levels were significantly increased in carcinoma of the tongue. A positive correlation was observed between HIF-1 alpha mRNA levels and pathological differentiation grade. A significant difference in the levels of HIF-1 alpha expression was detected between groups of patients with lymph node metastases and patients with no metastases. These results indicate that overexpression of HIF-1 alpha may be an indicator of poor prognosis in carcinoma of the tongue. The expression of HIF-1 alpha may be associated with lymph node metastasis.