Genomic and immunophenotypical differences between hepatocellular carcinoma with and without cirrhosis

Maria S. Tretiakova, Meer T. Shabani-Rad, Kelly Guggisberg, John Hart, Robert A Anders, Zu Hua Gao

Research output: Contribution to journalArticle

Abstract

Aims: To compare the expression of genes involved in p53, Wnt/β-catenin, and retinoblastoma (Rb) 1 pathways between cirrhosis-associated hepatocellular carcinoma (HCC-C) and hepatocellular carcinoma arising in non-cirrhotic liver (HCC-NC). Methods and results: The gene expression profile was analysed using oligo-DNA arrays, and then validated at protein level in a tissue microarray using immunohistochemistry. Compared with their background non-neoplastic liver tissue, HCC-C showed a significantly higher rate of p53, β-catenin (protein only) and cyclin D1 expression, whereas HCC-NC showed a significantly higher rate of p21Waf1/cip1 and p27Kip1 expression. HCC-C had a significantly higher rate of p53 expression and a significantly lower rate of p21waf1/cip1 expression than HCC-NC. There was no statistically significant association between the expression of genetic markers and tumour histological grade, underlying aetiology, or lymphovascular invasion. Aberrant β-catenin expression was more commonly seen in single tumours in comparison with multiple tumours. Increased p16INK4 and p21waf1/cip1 expression was more commonly observed in large-sized tumours (>50 mm) than small-sized tumours. Conclusions: Alteration of the p53 pathway plays a more important role in the pathogenesis of HCC-C, whereas alterations in cell cycle regulators p21 waf1/cip1 and p27Kip1 play a more important role in the pathogenesis of HCC-NC.

Original languageEnglish (US)
Pages (from-to)683-693
Number of pages11
JournalHistopathology
Volume56
Issue number6
DOIs
StatePublished - 2010

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Hepatocellular Carcinoma
Fibrosis
Catenins
Neoplasms
Cyclin-Dependent Kinase Inhibitor p21
Retinoblastoma
Liver
Cyclin D1
Oligonucleotide Array Sequence Analysis
Genetic Markers
Transcriptome
Immunohistochemistry
Gene Expression
Proteins

Keywords

  • Carcinogenesis
  • Cirrhosis
  • Gene profiling
  • Hepatocellular carcinoma
  • Tissue microarray

ASJC Scopus subject areas

  • Histology
  • Pathology and Forensic Medicine
  • Medicine(all)

Cite this

Genomic and immunophenotypical differences between hepatocellular carcinoma with and without cirrhosis. / Tretiakova, Maria S.; Shabani-Rad, Meer T.; Guggisberg, Kelly; Hart, John; Anders, Robert A; Gao, Zu Hua.

In: Histopathology, Vol. 56, No. 6, 2010, p. 683-693.

Research output: Contribution to journalArticle

Tretiakova, Maria S. ; Shabani-Rad, Meer T. ; Guggisberg, Kelly ; Hart, John ; Anders, Robert A ; Gao, Zu Hua. / Genomic and immunophenotypical differences between hepatocellular carcinoma with and without cirrhosis. In: Histopathology. 2010 ; Vol. 56, No. 6. pp. 683-693.
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AU - Anders, Robert A

AU - Gao, Zu Hua

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N2 - Aims: To compare the expression of genes involved in p53, Wnt/β-catenin, and retinoblastoma (Rb) 1 pathways between cirrhosis-associated hepatocellular carcinoma (HCC-C) and hepatocellular carcinoma arising in non-cirrhotic liver (HCC-NC). Methods and results: The gene expression profile was analysed using oligo-DNA arrays, and then validated at protein level in a tissue microarray using immunohistochemistry. Compared with their background non-neoplastic liver tissue, HCC-C showed a significantly higher rate of p53, β-catenin (protein only) and cyclin D1 expression, whereas HCC-NC showed a significantly higher rate of p21Waf1/cip1 and p27Kip1 expression. HCC-C had a significantly higher rate of p53 expression and a significantly lower rate of p21waf1/cip1 expression than HCC-NC. There was no statistically significant association between the expression of genetic markers and tumour histological grade, underlying aetiology, or lymphovascular invasion. Aberrant β-catenin expression was more commonly seen in single tumours in comparison with multiple tumours. Increased p16INK4 and p21waf1/cip1 expression was more commonly observed in large-sized tumours (>50 mm) than small-sized tumours. Conclusions: Alteration of the p53 pathway plays a more important role in the pathogenesis of HCC-C, whereas alterations in cell cycle regulators p21 waf1/cip1 and p27Kip1 play a more important role in the pathogenesis of HCC-NC.

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