The prevalence of human liver cancer shows a broad spectrum of variation in
distinct geographical regions, depending on different risk factors, and th
eir pathogenesis is poorly understood. We study the significance of molecul
ar alterations of K-ras gene inhuman liver carcinomas in a low-incidence re
gion such as a Mediterranean area of Spain (Valencia and Gerona). Our resul
ts reveal a low incidence of K-ras codon 12 mutations in hepatocellular car
cinomas (HCC) and a higher incidence in cholangiocarcinomas (CCC). Similar
results have been obtained in high-risk areas. We conclude that K-ras gene
mutations are not a major event in the malignant transformation of hepatic
cells in this region of the Mediterranean but that molecular implications o
f hepatocellular and cholangiocarcinomas appear to be different.