The clinical significance of splice variants and subcellular localisation of survivin in non-small cell lung cancers

Survivin is a member of the inhibitor of apoptosis protein family. Survivin has splice variants with different biological functions associated with tumorigenesis. We investigated 134 non- small cell lung cancers ( NSCLCs) to study the clinical significance of wildtype survivin, survivin- 2B, and survivin- deltaEx3. Real- time PCR analyses were performed for their gene expressions. The subcellular localisation of survivin proteins was evaluated by immunohistochemistry. The Ki- 67 proliferation index and the apoptotic index were also evaluated. The survivin- deltaEx3 gene expression was significantly higher in stage II - III than in stage I ( P = 0.0174), and significantly correlated with the nuclear pan- survivin expression ( P < 0.0001). The Ki- 67 index was significantly higher in wild- type survivin- positive tumours ( P < 0.0001), survivin- deltaEx3- positive tumours ( P < 0.0001), and tumours with positive expression of the nuclear pan-survivin ( P =0.0047). In contrast, the apoptotic index was significantly lower only in wild- type survivin- positive tumours ( P < 0.0001). Thus, the wild- type survivin gene expression was associated with apoptotic inhibition and tumour proliferation. Furthermore, the survivin- deltaEx3 gene expression was strongly associated with tumour proliferation, especially in advanced stage NSCLCs. In contrast, the survivin- 2B gene expression did not correlate with tumour proliferation or tumour apoptosis.