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Decreased immunoexpression of survivin could be a potential marker in human non-alcoholic fatty liver disease progression?.
Stefano, Jose T. 1; de Oliveira, Claudia P. M. S. 1; Correa-Giannella, Maria L. 2; Soares, Ibere C. 3; Kubrusly, Marcia S. 1; Bellodi-Privato, Marta 3; de Mello, Evandro S. 3; de Lima, Vicencia M. R. 1; Carrilho, Flair J. 1; Alves, Venancio A. F. 3
[Article] Liver International. 31(3):377-385, March 2011.

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Background/aim: Regulation of apoptosis in non-alcoholic fatty liver disease (NAFLD) has been a theme of growing debate. Although no other study assessed the role of survivin in NAFLD, its expression has been reported in hepatic carcinogenesis because of other aetiological factors with relevant discrepancies. The aim of this study was to assess the pattern of survivin immunoexpression by tissue microarray along the whole spectrum of NAFLD, including non-alcoholic steatohepatitis (NASH)-related hepatocelular carcinoma (HCC).

Methods: Liver biopsies from 56 patients with NAFLD were evaluated: 18 with steatosis, 21 non-cirrhotic NASH, 10 NASH-related cirrhosis, seven NASH-related HCC, as compared with 71 HCC related to other causes and with 12 normal livers.

Results: Survivin immunoexpression in NAFLD was restricted to cytoplasm and was found to be progressively lower in advanced stages, including cirrhosis and HCC: steatosis vs NASH-related cirrhosis (P=0.0243); steatosis vs NASH-related HCC (P=0.0010); NASH vs NASH-related cirrhosis (P=0.0318); and NASH vs NASH-related HCC (P=0.0007), thus suggesting a deregulation of apoptosis from NAFLD towards HCC. Interestingly, survivin immunoreactivity in NASH-related HCC was also found to be significantly lower than in HCC related to other causes (P<0.05). Remarkably, nuclear staining for survivin was not detected in any case of NAFLD, contrasting to its presence in all other cases of HCC.

Conclusions: Survivin immunoexpression in NASH-related HCC is herein originally found substantially different than in HCC related to other causes, thus requiring further studies to elucidate the role of survivin in human NAFLD progression.