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© 1992 Oxford University Press

other

Association between expression of transforming growth factor-alpha and progression of hepatocellular foci to neoplasms

William K. Kaufmann, Yingchun Zhang and David G. Kaufman

Department of Pathology and Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill Chapel Hill, NC 27599-7295, USA

Hepatocarcinogenesis was initiated in rats with a single dose of either of two chemical mutagens—benzo[{alpha}]pyrene diolepoxide I and methyl(acetoxymethyl)nitrosamine-administered 15 h after hepatectomy.The development of hepatocellular foci and neoplasms was then promoted with dietary phenobarbital given for 45 or 62 weeks. Formalin-fixed tissue specimens that contained hepatic neoplasms and altered hepatocellular foci were screened for expression of the oncodevelopmental marker glutathione-S-transferase (placental form) (GSTP) and transforming growth factor-alpha (TGF-alpha) using immunnohistchemistry. AN (100%) hepatocellular carcinomas expressed both GSTP and TGF-alpha, as did most hepatocellular adenomas (>80%). However, quantitative stereologic analysis of treated and control livers revealed that GSTP-postive foci were 10–30 times more frequent than TGF-alpha-positive foci. Foci with homogeneous expression of GSTP generally displayed heterogeneous expression of TGF-alpha with reaction product most prominent at their peripheries. Less frequently homogeneous TGF-alpha-positive foci were seen within GSTP-positive foci. The average volumes of those GSTP-positive foci that also expressed TGF-alpha were significantly greater than those of the entire sets of GSTP-positive foci. These results suggest that expression of TGF-alpha may distinguish a subset of Gm-positive foci that have a growth advantage and increased probability of progrrssion to neoplasia.


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