Immunohistochemical localization of survivin in benign cervical mucosa, cervical dysplasia, and invasive squamous cell carcinoma

Survivin is an inhibitor of apoptosis protein (IAP) that is expressed in fetal development and in cancer. Survivin expression in premalignant lesions remains undefined. We obtained 73 samples of cervical squamous tissue, including 31 normal, 17 low- and 15 high-grade squamous intraepithelial lesions (LSILs, HSILs), and 10 squamous cell carcinomas (SCCs) from cone biopsy and hysterectomy specimens, and stained for survivin using an immunoperoxidase method. Nuclear staining was detected in normal mucosa, LSILs, and HSILs; staining intensity was greatest in cases with morphologic evidence of human papillomavirus (HPV) infection. In situ hybridization of serial sections demonstrated colocalization of HPV DNA and survivin. Cytoplasmic staining was observed in immature squamous metaplasia and in SCCs. Survivin expression in immature metaplastic squamous mucosa may reflect a role for survivin in normal squamous differentiation. However, the histologic correlation between nuclear staining and HPV infection suggests involvement of survivin in HPV-mediated disruption of normal cellular maturation.