Background/Aims: Laminins, the major non-collagenous basement membrane components, are involved in various biological processes. Laminin isoforms have never been characterized in human livers. The expression of five laminin mRNA was investigated in livers with or without cancer and in hepatoma cells and, by comparison, in both rat hepatoma and hepatic stellate cells. Methods: Laminin α1, α2, β1, β2 and γ1 mRNA was detected by northern blot and/or RT-PCR in livers without chronic disease (n=5), in both tumoral and non-tumoral areas of livers with hepatocellular carcinomas (n=13) or metastases (n=18), in human HBGC2 and rat Faza-567 hepatoma cell lines, and in 6-day-old rat hepatic stellate cell cultures. Results: Laminin α1, α2 and β1 mRNA were found in 25–33% and γ1 mRNA in 58% of the livers, the signal for laminin β2 mRNA being faint in all the samples. Laminin α2, β1, β2 and γ1 mRNA were expressed in hepatoma and stellate cells. The laminin α2 cDNA probe recognized a 3.5 kb mRNA different from the expected 9 kb mRNA. Using degenerated oligonucleotides, RT-PCR products from both rat hepatoma and stellate cells revealed 90% identity with the α2 chain sequence. Antibodies against peptide deduced from the conserved C-terminal domain of both α1 and α2 chains recognized polypeptides corresponding to the degradation products of α2 chain in liver extracts and both media and cell layers from hepatoma and stellate cells. In addition, a Mr=130 000 polypeptide was revealed by these antibodies in liver extracts and cell layers, which was consistent with the expected size deduced from the 3.5 kb mRNA. Conclusions: This first report on laminin isoforms in human livers indicates that laminin 1 (α1-β1-γ1), 2 (α2-β1-γ1), 3 (α1-β2-γ1) and 4 (α2-β2-γ1) mRNA and a polypeptide homologous to the α2 isoform, which could correspond to a truncated form of this chain, are usually expressed in non-tumoral and/or tumoral livers.

Background/Aims: Laminins, the major non-collagenous basement membrane components, are involved in various biological processes. Laminin isoforms have never been characterized in human livers. The expression of five laminin mRNA was investigated in livers with or without cancer and in hepatoma cells and, by comparison, in both rat hepatoma and hepatic stellate cells.Methods: Laminin alpha 1, alpha 2, beta 1, beta 2 and gamma 1 mRNA was detected by northern blot and/or RT-PCR in livers without chronic disease (n=5), in both tumoral and non-tumoral areas of livers with hepatocellular carcinomas (n=13) or metastases (n=18), in human HBGC2 and rat Faza-567 hepatoma cell lines, and in 6-day-old rat hepatic stellate cell cultures.Results: Laminin alpha 1, alpha 2 and beta 1 mRNA were found in 25-33% and gamma 1 mRNA in 58% of the livers, the signal for laminin beta 2 mRNA being faint in all the samples. Laminin alpha 2, beta 1, beta 2 and gamma 1 mRNA were expressed in hepatoma and stellate cells. The laminin alpha 2 cDNA probe recognized a 3.5 kb mRNA different from the expected 9 kb mRNA. Using degenerated oligonucleotides, RT-PCR products from both rat hepatoma and stellate cells revealed 90% identity with the alpha 2 chain sequence. Antibodies against peptide deduced from the conserved C-terminal domain of both al and alpha 2 chains recognized polypeptides corresponding to the degradation products of alpha 2 chain in liver extracts and both media and cell layers from hepatoma and stellate cells. In addition, a Mr=130000 polypeptide was revealed by these antibodies in liver extracts and cell layers, which was consistent with the expected size deduced from the 3.5 kb mRNA.Conclusions: This first report on laminin isoforms in human livers indicates that laminin 1 (alpha 1-beta 1-gamma 1), 2 (alpha 2-beta 1-gamma 1), 3 (alpha 1-beta 2-gamma 1) and 4 (alpha 2-beta 2-gamma 1) mRNA and a polypeptide homologous to the alpha 2 isoform, which could correspond to a truncated form of this chain, are usually expressed in non-tumoral and/or tumoral livers.

A case of hepatic mesenchymal hamartoma, found after sudden onset clinical and biological cholestasis, is reported in a 18-year-old man. Abdominal ultrasound examination and computed tomography showed a intrahepatic cystic tumor. The diagnosis of hepatic mesenchymal hamartoma was made by the pathological examination of the resected specimen. This rare tumor is found in most cases in children less than 2 years old. Thirteen cases in adulthood were already reported, five of them in Japanese patients. Our case is peculiar because no hepatic tumor was shown by ultrasound examination, 2 years before, the large size of cysts and presence of smooth muscle fibers in the wall.

A case of hepatic mesenchymal hamartoma, found after sudden onset clinical and biological cholestasis, is reported in a 18-year-old man. Abdominal ultrasound examination and computed tomography showed a intrahepatic cystic tumor. The diagnosis of hepatic mesenchymal hamartoma was made by the pathological examination of the resected specimen. This rare tumor is found in most cases in children less than 2 years old. Thirteen cases in adulthood were already reported, five of them in Japanese patients. Our case is peculiar because no hepatic tumor was shown by ultrasound examination, 2 years before, the large size of cysts and presence of smooth muscle fibers in the wall.

Iron was systematically studied in the nontumorous liver of 24 patients with hepatocellular carcinoma (HCC) developed on a noncirrhotic liver compared with 4 control groups (cirrhosis with and without HCC, liver metastasis, and normal liver) matched according to age, sex, and presence of chronic alcoholism. Assessment of liver iron was made by (1) histology according to iron distribution and quantification (total iron score: 0 to 60), and (2) biochemistry (liver iron concentration-N < 36 mumol/g) with calculation of the hepatic iron index (liver iron concentration/age). Patients with hepatocellular carcinoma developed on a noncirrhotic liver presented with (1) histological iron in 83%; (2) parenchymal iron excess significantly more frequent (90%) than in controls; (3) total iron score (15 +/- 12) and liver iron concentration (81 +/- 96) significantly greater than in controls; and (4) hepatic iron index significantly increased (1.4 +/- 1.5) when compared with control groups, except for the hepatocellular carcinoma complicating cirrhosis group (0.9 +/- 1.1). This study (1) shows a mild but unquestionable parenchymal iron excess in the nontumorous liver of most patients presenting with hepatocellular carcinoma developed on a noncirrhotic liver and, at a lesser extent, on cirrhosis, (2) should incite others to study the putative role of iron in the development of liver cancer both in patients with cirrhosis and those without it, whatever the cause of the underlying liver disease, and (3) add argument to take into account and to treat any liver iron excess, even when mild.