Document Detail

Novel markers of cell kinetics to evaluate progression from cirrhosis to hepatocellular carcinoma.
MedLine Citation:
PMID:  16629645     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: We investigated cell cycle kinetics of nodular lesions in cirrhosis to differentiate hepatocellular carcinoma (HCC) from its precursor lesions. METHODS: Twelve small HCC, 10 regenerative (RN), six large regenerative (LRN), and five dysplastic nodules (DN), identified in explant cirrhotic livers of five consecutive patients transplanted at Royal Free Hospital in 2002. Immunoperoxidase for MCM2, geminin and Ki67 was performed and the percentage of positive cells counted. RESULTS: The proportion of cells expressing MCM2 was more than those expressing Ki67, which in turn was more than those expressing geminin (overall median=16%, 2% and 0.5%, respectively, P<0.001). There was a statistically significant trend of increasing Ki67 expression (P=0.006), from RN to HCC; this trend was not statistically significant for geminin (P=0.18) or MCM2 (P=0.51). The median percentage of cells expressing Ki67 was 1% in RN, 0.5% in LRN, 2.2% in DN and 5.4% in HCC. The combination of these markers identified four different cell kinetics patterns: 'resting' (G0 cells: MCM2 -ve, Ki67 -ve, geminin -ve); 'licensed' (MCM2 +ve, Ki67 -ve, geminin -ve); 'slowly growing' (G1 phase arrest, MCM2 +ve, Ki67 +ve, low (0.4%) geminin) and expanding (MCM2 +ve, Ki67 +ve, geminin +ve) nodules. CONCLUSIONS: The combination of MCM2, geminin and Ki67 could represent a valuable tool in the understanding of HCC progression in cirrhosis.
Alberto Quaglia; Mary McStay; Kai Stoeber; Marco Loddo; Martyn Caplin; Thomas Fanshawe; Gareth Williams; Amar Dhillon
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Liver international : official journal of the International Association for the Study of the Liver     Volume:  26     ISSN:  1478-3223     ISO Abbreviation:  Liver Int.     Publication Date:  2006 May 
Date Detail:
Created Date:  2006-04-24     Completed Date:  2006-09-15     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101160857     Medline TA:  Liver Int     Country:  England    
Other Details:
Languages:  eng     Pagination:  424-32     Citation Subset:  IM    
Department of Histopathology, Royal Free and University College Medical School, London, UK.
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MeSH Terms
Biological Markers
Carcinoma, Hepatocellular / genetics,  metabolism,  physiopathology*
Cell Cycle*
Cell Cycle Proteins / genetics,  metabolism
Cell Transformation, Neoplastic
Disease Progression
Gene Expression Regulation
Gene Expression Regulation, Neoplastic
Ki-67 Antigen / genetics,  metabolism
Liver Cirrhosis / genetics,  metabolism,  physiopathology*
Liver Neoplasms / genetics,  metabolism,  physiopathology*
Middle Aged
Nuclear Proteins / genetics,  metabolism
Reg. No./Substance:
0/Biological Markers; 0/Cell Cycle Proteins; 0/GMNN protein, human; 0/Ki-67 Antigen; 0/MCM2 protein, human; 0/Nuclear Proteins

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