Survivin expression predicts poorer prognosis in patients with areca quid chewing-related oral squamous cell carcinoma in Taiwan.

Survivin, a recently characterized novel member of the inhibitor of apoptosis (IAP) family, is not detectable in most differentiated normal adult tissues but is expressed in a wide range of cancer tissues. Its expression in cancer has been correlated with poor prognosis, cancer progression and drug resistance. We immunohistochemically examined the expression of survivin in 62 cases of oral epithelial dysplasia (ED) and 96 cases of oral squamous cell carcinoma (SCC). Cytoplasmic survivin staining was detected in 60 of the 62 (97%) ED specimens and 94 of the 96 (98%) SCC specimens but not in adjacent normal oral mucosal tissues. The labeling index (LI) for survivin protein significantly increased from ED (32.3+/-16.3%) to SCC samples (49.4+/-28.5%) (p<0.001). In addition, the mean LI for ED cases with further malignant transformation into SCC (45.6+/-8.8%) was higher than those without malignant transformation (30.1+/-16.3%) (p=0.008). No significant correlation was found between the survivin expression and the patients' age, sex, oral habit, cancer location, or STNM status in SCC cases. Kaplan-Meier curves showed oral SCC patients with high survivin expression (LI>25%), advanced stage, larger tumor size, or positive lymph node metastasis had significantly shorter overall survival (p=0.014, 0.012, 0.005 and 0.011, respectively by log-rank test) than others. The associations remained significant after adjusting for age. These results indicate that survivin protein expression may be an important early event in oral carcinogenesis and predicts unfavorable prognosis for oral SCC. Furthermore, the unique expression of survivin in cancer cells but not in most normal adult tissues suggests that modulation of survivin protein expression may provide a novel strategy for the therapy of oral SCC.