Expression of Survivin and Caspase-3 in Oral Cancer

Objectives: Survivin and caspase-3 are two proteins that regulate programmed cell death (apoptosis) as well as angiogenesis. This immunohistochemical study examined the expression of survivin and caspase-3 and their spatial association with apoptosis and angiogenesis in the process of oral mucosal carcinogenesis. Methods: 45 tissue specimens comprising 16 of oral leukoplakia with mild to moderate epithelial dysplasia, 12 of leukoplakia with severe epithelial dysplasia, 17 of moderate to well differentiated oral squamous cell carcinoma and 10 normal mucosa specimens were investigated. Survivin and caspase-3 were detected by immunohistochemistry. Apoptosis was identified by the terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assay. Microvessel density was determined by immunostaining using factor VIII. Results: Survivin expression level was increased significantly with greater severity of epithelial dysplasia, while caspase-3 levels decreased at the same time. The apoptosis index decreased significantly with the progression of epithelial dysplasia. Microvessel density was increased significantly from normal mucosal tissues to oral squamous cell carcinoma tissue, reflecting angiogenic activity to meet the greater growth needs at the site. Conclusions: Caspase 3 expression appears to be associated inversely with the severity of dysplasia. As survivin expression increased, caspase-3 expression and the apoptosis index decreased. Survivin may inhibit cell apoptosis by modulating caspase-3 expression, and these markers may have potential value in predicting prognosis. Enhanced expression of survivin may also facilitate neomicrovessel formation, which could play a role in the process of carcinogenesis and in particular metastatic spread of oral squamous cell carcinoma.