Survivin overexpression in HCC and liver cirrhosis differentially correlates with p-STAT3 and E-cadherin

Abstract

Survivin, a member of the family of inhibitorof apoptosis proteins, functions as a key regulator ofapoptosis and cell proliferation. Overexpression ofsurvivin has been implicated in several human cancers,including human hepatocellular carcinoma (HCC).Although several factors have been shown in vitrotoupregulate survivin expression in cancer cells, the invivoregulators of survivin in human hepato-carcinogenesis are largely unknown. We studied byimmunohistochemistry the protein expression ofsurvivin in relation to cyclin D1, phosphorylated signaltransducer and activator of transcription 3 (p-STAT3), ß-catenin, E-cadherin and phosphorylated-Akt (p-Akt) in69 cases of HCC and adjacent liver cirrhosis. Survivinwas expressed in 63/69 (91.3%) cases of HCC and in40/47 (85.1%) cases of liver cirrhosis. Survivinlocalization in HCC was exclusively nuclear, whileintense cytoplasmic and low nuclear expression ofsurvivin was observed in cases of cirrhosis. Survivinexpression in HCC correlated significantly with lowgrade tumors, expression of cyclin D1 and p-STAT3.Expression of survivin in liver cirrhosis correlated withdownregulation of E-cadherin expression. There was nosignificant correlation of survivin with ß-catenin or p-Akt in HCC or liver cirrhosis. In conclusion, we showedan association of nuclear survivin with welldifferentiated HCC, as well as with the expression of thecell cycle regulator cyclin D1. Activation of STAT3 andloss of E-cadherin but not ß-catenin or Akt pathwaysseem to be implicated in survivin upregulation in HCCand liver cirrhosis.