INCREASED HEPATIC FERRITIN-H MESSENGER-RNA LEVELS CORRELATE WITH THOSE OF C-MYC IN HUMAN HEPATOCELLULAR-CARCINOMA

Serum ferritin is elevated in many cancers. Using the subtraction-enha nced display technique, we isolated several cDNA clones including ferr itin-H which is overexpressed in rat hepatocellular carcinoma (HCC) in duced by diethylnitrosamine. We investigated hepatic messenger RNA (mR NA) levels of ferritin-H in patients with HCC, adenoma, cirrhosis and healthy controls in relation to those of oncogene c-myc. Ferritin-H mR NA levels were 2-12 fold higher in tumor tissues than in adjacent non- tumor tissues in 12 of 17 patients with HCC, irrespective of coexistin g cirrhosis or viral hepatitis. However, no difference in ferritin-H m RNA levels was found in patients with adenoma, cirrhosis and healthy c ontrols. c-myc mRNA levels were 2-5 ford increased in 11 of 17 HCC pat ients, and correlated significantly with those of ferritin-H (p<0.001) . In situ hybridization showed that the overexpressed ferritin-H mRNA was restricted to the tumor nodules in HCC livers. These findings sugg est that overexpression of ferritin-fl in HCC patients, correlated wit h c-myc, is phenotypically associated with HCC, and could become a use ful molecular indicator for human HCC.