Nuclear survivin is associated with cell proliferative advantage in uterine cervical carcinomas during radiation therapy

Background Although the anticancer effects of radiation therapy for patients with uterine cervical squamous cell carcinoma (U-SCC) are widely acknowledged, little is known about the resultant morphological alterations in tumour tissue kinetics.

Aims To make a detailed assessment of possible roles of survivin expression in apoptosis and cell proliferation in U-SCC during radiation therapy.

Methods 181 biopsy specimens from 55 consecutive U-SCCs of patients receiving radiation therapy were studied using a combined morphological (apoptosis) and immunohistochemical (MIB-1 and survivin) approach. The intracellular distribution of various splice variants of the survivin gene was also examined.

Results Tumour cell proliferation, determined as MIB-1 labelling indices (LIs), as well as nuclear survivin (N-Surv) LIs, were inversely correlated with irradiation dosage, in contrast to relatively minor changes in apoptotic indices, suggesting a shift in tumour tissue kinetics towards a relative predominance of cell deletion. In addition, the low N-Sur LI category showed significant stepwise decrease in MIB-1 LIs during therapy, in contrast to no changes in the high category. Exogenous overexpression of three variants of the survivin gene resulted in different expression patterns, showing cytoplasmic staining with or without dot formation for survivin and survivin-2B and distinct nuclear accumulation for survivin-deled exon 3 (∆Ex3).

Conclusions Results showed that nuclear survivin, including survivin itself and the survivin-∆Ex3 splice variants, may participate in modulation of altered cell kinetics of U-SCC during radiation therapy.