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Virchows Arch (2011) 459:129139 DOI 10.1007/s00428-011-1103-0
ORIGINAL ARTICLE
Clinical significance of histone deacetylases 1, 2, 3, and 7: HDAC2 is an independent predictor of survival in HCC
Karl Quint & Abbas Agaimy & Pietro Di Fazio & Roberta Montalbano &
Claudia Steindorf & Rudolf Jung & Claus Hellerbrand & Arndt Hartmann &
Helmut Sitter & Daniel Neureiter & Matthias Ocker
Received: 28 February 2011 /Revised: 4 May 2011 /Accepted: 30 May 2011 /Published online: 29 June 2011 # Springer-Verlag 2011
Abstract Histone deacetylases (HDAC) are responsible for the transcriptional control of genes through chromatin remodeling and control tumor suppressor genes. In several tumors, their expression has been linked to clinicopatho-logical factors and patient survival. This study investigates HDACs 1, 2, 3, and 7 expressions in hepatocellular carcinoma (HCC) and their correlation with clinical data and patient survival. Tissue microarrays of 170 surgically resected primary HCCs and adjacent uninvolved tissue
were evaluated immunohistochemically for the expression of HDACs 1, 2, 3, 7, and Ki-67 and were analyzed with respect to clinicopathological data and patient survival. HDACs 1, 2, 3, and Ki-67 were expressed significantly higher in cancer cells compared to normal tissue (HDAC1: p=0.034, HDACs 2 and 3 and Ki-67: p<0.001), while HDAC7 expression did not differ between HCC and non-cancerous liver tissue. In tumor tissue HDACs 13 expression levels showed high concordance with each other, Ki-67 and tumor grade (p<0.001). High HDAC2 expression was associated with poor survival in low-grade and early-stage tumors (p<0.05). The expression of the HDACs 1, 2, and 3 (but not HDAC7) isoenzymes correlates with clinicopathological factors, and HDAC2 expression has an impact on patient survival.
Keywords Correlation analysis . Expression analysis . Hepatocellular carcinoma . Histone deacetylases . Overall survival . Tissue microarray
Introduction
Hepatocellular carcinoma (HCC) belongs to the most common tumor diseases worldwide, and its incidence is increasing in industrial nations [1, 2]. The causes for HCC are diverse and include chronic viral hepatitis, heavy alcohol use, or metabolic diseases such as hemochromatosis. The diversity of the pathophysiological processes that results from these different etiological factors makes HCC a heterogeneous tumor [3]. Curative therapies, such as liver resection and transplantation, are possible in only 15% of patients, but recurrence rates are high. Those not eligible for
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