Expression of hypoxia-inducible factor-1 alpha is significantly associated with the progression and prognosis of oral squamous cell carcinomas in Taiwan.

ABSTRACT

BACKGROUND: Overexpression of hypoxia-inducible factor-1 alpha (HIF-1 alpha) has been found to be significantly associated with the tumor invasion, lymph node metastasis, clinical stage, and prognosis of a variety of human cancers. METHODS: This study examined the expression of HIF-1 alpha in 57 specimens of oral squamous cell carcinoma (OSCC), 41 specimens of oral epithelial dysplasia (OED, 12 mild, 17 moderate, and 12 severe OED cases), and 14 specimens of normal oral mucosa (NOM) by immunohistochemistry. RESULTS: We found that the mean nuclear HIF-1 alpha labeling indices (LIs) increased significantly from NOM (9 +/- 6%) through mild OED (25 +/- 18%), moderate OED (41 +/- 27%), and severe OED (42 +/- 22%) to OSCC samples (55 +/- 23%, P < 0.001). A significant correlation was found between the higher mean nuclear HIF-1 alpha LI and OSCCs with larger tumor size (P < 0.001), regional lymph node metastasis (P < 0.001), or more advanced clinical stages (P < 0.001). Only larger tumor size (P = 0.002) and nuclear HIF-1 alpha LI >or= 60% (P = 0.048) were identified as independent unfavorable prognosis factor by multivariate analyses with Cox regression model. Kaplan-Meier curve showed that OSCC patients with a nuclear HIF-1 alpha LI >or= 60% had a significantly poorer cumulative survival than those with a nuclear HIF-1 alpha LI < 60% (log-rank test, P = 0.022). CONCLUSIONS: We conclude that the expression of HIF-1 alpha is an early event in oral carcinogenesis. The nuclear HIF-1 alpha LI in OSCC samples can predict the progression of OSCCs and the survival of OSCC patients.