119 TRANSFERRIN RECEPTOR EXPRESSION IN HUMAN HEPATOCELLULAR CARCINOMA.

R. Sciot |, P. Van Eyken |, A.C. Paterson 2, F. Callea 3, M.C. Kew 4, V.J. Desmet 1 Departments of Pathology, IUniversity of Leuven, Belgium, ZSouth African Insti- tute for Medical Research, Johannesburg, 3Spedali Civil| di Brescia, Italy and 4Department of Medicine, Witwatersrand Medical School, Johannesburg.

In general, expression of the transferrin receptor (TfR) is related to cell prolifera- tion and/or activated cell metabolism. Using TfR immunohistochemistry, various types of tumors were found to display intense TfR expression. In some tumors (lymphoma, breast ca, cervical malignancy) TfR expression seemed to correlate with tumor grading.

Using an indirect i~unoperoxidase technique on frozen sections with a panel of 5 mono- clonal anti TfR antibodies, we investigated the TfR expression in 34 hepatocellular carci- nomas (HCC's) of Belgian (n=6), Italian (n=7) and South African (n=2|) origin, which were classified as well, moderately and poorly differentiated. 33/34 HCC's showed an intense TfR immunostain. In 15 specimens also containing non-tumoral liver tissue, 2 of which in- cluded dysplastic areas, tumor staining was more intense than the surrounding parenchyma. In HCC cells, immunoreactivity was usually membranous and cytoplasmic; a more intense im- munoreaction on the cells oriented towards the stroma or around blood vessels was frequent~ observed. One HCC showed a weaker staining. This aberrant TfR expression may be related to the intense inflammation and the remarkable positivity for hepatitis B core and surface antigen in the tumor cells. No relation was observed between the degree of tumor differen- tiation and the pattern or intensity of staining.

In view of the increasing detection of minute HCC's, strong TfR expression in tumor cells may be of additional help in identifying small, early loci of HCC amongst cirrhotic nodules.

120 EFFECTS OF GLUCAGON ON HEPATIC AND SYSTEMIC HAEMODYNAMICS IN PATIENTS WITH CIRRHOSIS AND PORTAL HYPERTENSION G, Si lva, J.Chesta, J.Bosch, R.Mastai, M.Navasa, D.Kravetz, R.Casamltjana, J . ~ Liver Unit, Hospital C l in i c i Provlnc ia l , Un ivers i ty of Barcelona

I t has been suggested that glucagon plays an important role in the pathogenesis of portal hypertension. Thls is based in the fact that glucagon causes splanchnic vasodilation and is markedly increased in cirrhosis. The present study was aimed at comparing the haemodynamic effects of a pharmacological dose of glucagon (l mg IV) in patients with cirrhosis (n=lO) and in subjects without l iver disease (controls, n=5). Prior, and 3, 6, 9, 15 and 30 min after glucagon administration the followlng were measured: portal pressure (as WHVP-FHVP), mean arterial pressure (MAP), heart rate (HR) and cardlac output (CO, thermodilution). In addltion, in patients with cirrhosls, azygos blood flow (AzBF, continuous thermodilution) was also measured. Plasma glucagon was measured by RIA. In patients with cirrhosis, glucagon administrat ion increased HR by 7±1% (p,O,Ol), CO by 6±1% (p~O.05) and MAP by 6±2% (p<O.05). These systemic ef fects were acompanied in the splanchnic c i r cu la t i on by a s i gn i f i can t increase in AzBF (from 538+28 to 641±39 ml/min, p<0.025) and portal pressure (from 18.1+1.2 to 19.0+I.2 mmHg, p<O. Ol)~ In subjects without portal hypertension, HR increased by 18+4% (p<O.05~, CO by 16+4% (p<O.05) and MAP by 13+4% (p<O.05). These changes were s i g n i f i c a n t l y greater than those observed in pat ients with ~ i r rhos is (~0 .05 ) . The observation that base- l i ne plasma glucagon was much higher in c i r rho t i cs (837±179 pg/ml) than in controls (200+27 pg/ml, p<O. Ol) suggest that the resistance to the haemodynamic ef fects of glucagon observed in pat ients wi th c i r rhos ls could be related to a down-regulation of vascular glucagon receptors promoted by the maintained increase in c i r cu la t i ng glucagon levels. In fact , there was a negative cor re la t ion between basal glucagon levels and the response of HR to glucagon in jec t ion (r=-0.57, p~O.05). The s i gn i f i can t increase in AzBF and portal pressure fo l lowing glucagon adminlstrat ion is consistent with the hypothesls that glucagon may contr ibute to the splanchnic vasodi lat ion and increased portal pressure of c i r rhos is .

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