Survivin immunohistochemical expression in hepatocellular carcinoma: Correlation with tumour differentiation and proliferation

Abstract 

Background and study aims

Recently, survivin was shown to inhibit apoptosis and accelerate cancer cell proliferation as well. The expression of survivin may be of prognostic significance and therapeutic relevance in many cancers. This study investigated the expression of survivin in hepatocellular carcinoma (HCC); correlated results with tumour differentiation and proliferation (topoisomerase II α) and compared the expression with the surrounding cirrhotic liver tissue.

Patients and methods

The expression of survivin and topoisomerase II α was evaluated by immunohistochemistry in 20 cases of HCC and 20 liver cirrhosis tissues. The relationships between two survivin scoring methods – topoisomerase II α nuclear labelling index (LI) and tumour differentiation – were analysed.

Results

Eighteen (90%) HCC cases expressed survivin. Median survivin nuclear LI was 75% and 6.5% in HCC and cirrhotic liver tissue, respectively. Median survivin weighted score was 8 and 0 in HCC and cirrhotic liver tissue, respectively. Survivin expression was significantly higher in HCC than in cirrhotic liver tissue (p<0.001). Median survivin expression L1 was 83% and the weighted score was 12 in moderately differentiated HCC versus 33% and 4, respectively in well-differentiated HCC with statistically significant p<0.001. Median topoisomerase II α LI was 22.5% and 3% in HCC and cirrhotic liver tissue respectively, with a statistically significant difference (p<0.001). Median topoisomerase II α was 27.5, 9% in moderately and well-differentiated HCC respectively, with a statistically significant difference (p<0.001). The increase in survivin nuclear expression in HCC correlates significantly with the increase in topoisomerase II α nuclear expression (p<0.001, r=0.987).

Conclusion

Both survivin scoring methods were sensitive in discriminating between studied groups; however, nuclear LI showed more specificity. Both survivin and topoisomerase II α expressions were significantly higher in HCC than in cirrhotic liver tissue and correlated significantly with tumour de-differentiation in HCC cases. Survivin nuclear LI correlated significantly with tumour cell proliferation.

Keywords: Survivin, Topoisomerase II α, Hepatocellular carcinoma