Linked Life Data

17460450

Source:http://linkedlifedata.com/resource/pubmed/id/17460450

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2007-4-26
pubmed:abstractText
The emergence of hepatocellular carcinoma (HCC) is thought to be a stepwise process, with high-grade dysplastic nodules (HGDN) representing premalignant lesions arising in a background of cirrhosis. Earlier studies have revealed altered expression of transforming growth factor-alpha (TGF-alpha) (a mitogen capable of inducing hepatocarcinogenesis in mice) in HCC and its surrounding parenchyma. DNA topoisomerase II-alpha (Topo II-alpha) is a nuclear protein targeted by several chemotherapeutic agents and is overexpressed in HCC. The expression of both TGF-alpha and Topo II-alpha in putative preneoplastic hepatocytic lesions, however, has not been extensively studied. We examined the patterns of TGF-alpha and Topo II-alpha expression in noncirrhotic liver, liver cirrhosis, low-grade dysplastic nodules (LGDN), HGDN, and HCC to define the possible relationships of these markers to tumor progression. Paraffin sections from formalin-fixed material were immunostained with antibodies against TGF-alpha, Topo II-alpha, and Ki-67. Forty-six HCC, 17 HGDN, and 12 low-grade dysplastic nodules were identified in 52 cirrhotic livers from explanted or resected specimens. Nuclear staining for Ki-67 and Topo II-alpha was significantly increased in the progression from cirrhosis, through HGDN, to HCC, whereas the scores for TGF-alpha in these lesions showed an inverse relationship. In comparison with 18 HCC arising in noncirrhotic livers, the expression of TGF-alpha is significantly stronger in cirrhotic liver than in noncirrhotic parenchyma and its expression is also stronger in HCC arising in cirrhosis than in HCC arising in noncirrhotic parenchyma. The increased expression of Topo II-alpha and Ki-67 from HGDN to HCC, when compared with cirrhosis, suggests that HGDN is a precursor lesion in hepatocarcinogenesis. The inverse relationship between these proliferative markers and TGF-alpha expression in these lesions and stronger expression of TGF-alpha in HCC arising in cirrhosis suggest that TGF-alpha may play an important role in the early events of liver carcinogenesis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0147-5185
pubmed:author
pubmed:issnType
Print
pubmed:volume
31
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
681-9
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
The expression of transforming growth factor-alpha in cirrhosis, dysplastic nodules, and hepatocellular carcinoma: an immunohistochemical study of 70 cases.
pubmed:affiliation
Department of Pathology, School of Medicine, University of Washington, Seattle, WA 98195-6100, USA. myeh@u.washington.edu
pubmed:publicationType
Journal Article