Significance of intracellular localization of survivin in cervical squamous cell lesions: Correlation with disease progression

Survivin is a member of the inhibitor of apoptosis protein family. Under normal circumstances, survivin is expressed in embryonic and fetal tissues, but is completely downregulated in normal adult tissues. Notably, this protein has been found to be prominently expressed in a variety of human malignant tumors. The present study was designed to evaluate the possible role of survivin in the tumorigenesis of cervical intraepithelial neoplasia and invasive squamous cell carcinoma (SCC) of the uterine cervix. In addition, it was investigated whether the nuclear or cytoplasmic expression of survivin is associated with tumor progression. In total, 71 samples of cervical squamous tissue were obtained, including 15 normal squamous epithelia, 25 high-grade squamous intraepithelial lesions (HSILs) and 31 SCCs, from cone biopsy and hysterectomy specimens and stained for survivin expression by immunohistochemistry. The intensity of survivin expression tended to increase with tumor progression (60.0% of normal mucosa, 76.0% of HSIL and 80.6% of SCC samples demonstrated high intensity survivin expression), but this correlation was not found to be statistically significant. However, a statistically significant difference was identified in the intracellular localization of survivin among the normal mucosa, HSIL and SCC samples (P<0.001). In total, 72% (18/25) of HSIL and 54.8% (17/31) of SCC cases expressed cytoplasmic staining in contrast to the nuclear staining of the normal mucosa. In addition, 64% (16/25) of HSIL and 42% (13/31) of SCC cases showed coexpression in the nucleus and cytoplasm. An inverse correlation was identified between the decrement of nuclear survivin expression and tumor progression, but was not statistically significant (P=0.08). These results indicated that analysis of the intracellular expression of survivin (particularly cytoplasmic expression) is a marker for predicting disease progression in the uterine cervix.