In vivo expression patterns of survivin and its splicing variants in chronic liver disease and hepatocellular carcinoma

Aim: Our aim was to clarify the significance of expression levels and post-transcriptional splicing patterns of survivin during multistep hepatocarcinogenesis and tumor progression. Methods: Using immunohistochemistry, we first elucidated the expression of survivin protein in tissues of hepatocellular carcinoma (HCC) and the adjacent non-cancerous tissues. Furthermore, we investigated survivin gene expression patterns in these tissues. Results: Survivin protein was expressed not only in most HCC tissues but also in some cirrhotic nodules. In non-cancerous regions, the levels of survivin mRNA increased in proportion to their stage of progression. Survivin protein was expressed mainly in periportal areas, where proliferating cells were localized. In HCC, mRNA levels of survivin and survivin DeltaEx3 correlated with high proliferative activity, whereas the levels of surviving 2B did not. Discussion: These findings of mRNA and protein expressions of survivin in chronically injured avers indicate that it has an important role in hepatocarcinogenesis. A lack of correlation between proliferative activity and survivin 2B mRNA levels in HCC is suggestive of a previous hypothesis that this variant decreases sruvivin function in a dominan negative manner. Thus, our data suggest different functions of these splicing variants and their important roles in tumor progression.