Genomic and immunophenotypical differences between hepatocellular carcinoma with and without cirrhosis.
OBJECTIVE
To compare the expression of genes involved in p53, Wnt/beta-catenin, and retinoblastoma (Rb) 1 pathways between cirrhosis-associated hepatocellular carcinoma (HCC-C) and hepatocellular carcinoma arising in non-cirrhotic liver (HCC-NC).


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, beta-catenin (protein only) and cyclin D1 expression, whereas HCC-NC showed a significantly higher rate of p21(Waf1/cip1) and p27(Kip1) expression. HCC-C had a significantly higher rate of p53 expression and a significantly lower rate of p21(waf1/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 beta-catenin expression was more commonly seen in single tumours in comparison with multiple tumours. Increased p16(INK4) and p21(waf1/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 p27(Kip1) play a more important role in the pathogenesis of HCC-NC.
Tretiakova
Maria S
MS
Department of Pathology, University of Chicago Hospitals, Chicago, IL, USA.
Shabani-Rad
Meer T
MT
Guggisberg
Kelly
K
Hart
John
J
Anders
Robert A
RA
Gao
Zu-Hua
ZH
D000328:Adult; D006528:Carcinoma, Hepatocellular / Q000209:etiology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D016130:Immunophenotyping; D008103:Liver Cirrhosis / Q000150:complications*; D008113:Liver Neoplasms / Q000209:etiology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism
D025521:Tumor Suppressor Proteins