The development of hepatocellular carcinoma in rodents treated with di
fferent chemical compounds is associated with the appearance in the cy
tosol of neoplastic liver cells of an unusual aldehyde dehydrogenase i
sozyme of class 3 (ALDH-3) which is very active with aromatic aldehyde
s. This tumor-associated isozyme is readily detected by enzyme cytoche
mistry using the substrate benzaldehyde with NADP as coenzyme. To dete
rmine whether human hepatocellular carcinomas express ALDH-3, the acti
vity of this isozyme was examined in frozen sections from 68 echo-guid
ed human liver biopsies. In 54 cases the guided biopsy was performed o
n one or more nodules suggestive for hepatocellular carcinoma found at
ultrasonography within the liver parenchyma. The remaining 14 patient
s were affected by chronic active hepatitis or cirrhosis. An intense e
nzymatic activity was ascertained in 5 out of 36 hepatocellular carcin
omas. In non-neoplastic liver, in macroregenerative nodules and in met
astatic adenocarcinomas enzymatic activity was not detectable. ALDH-3-
positive tumors were typical hepatocellular carcinomas (histological g
rade II and III). These results suggest that ALDH-3 is a phenotype ass
ociated with malignancy in human liver tumors.