Amplification of growth factor receptor genes and DNA ploidy pattern in the progression of gastric cancer

Abstract

 To study the background of oncogene amplification in gastric cancers, we examined the correlation between occurrence of oncogene amplification and DNA ploidy pattern. In 57 primary gastric cancers, amplifications of c-erbB, c-erbB-2, c-met and K-sam genes were investigated by Southern blot analysis, and the DNA ploidy pattern was determined by static cytofluorometry and by flow cytometry. Oncogene amplification was detected in 11 cancers, 10 of which were advanced gastric cancers and 1 was an early differentiated type. The amplification of c-erbB-2 and K-sam genes was found exclusively in differentiated- and undifferentiated-type cancers, respectively. Of the 11 cancers, 5 were DNA-diploid and 6 were DNA-aneuploid. All the 11 tumours with oncogene amplification contained polyploid cell populations (polyploidy), whereas none of the tumours without polyploidy showed oncogene amplification. In differentiated-type cancers the incidence of polyploidy was high in both early and advanced stages, while in undifferentiated-type cancers it was low in early stages but significantly higher in advanced stages. It was thus shown that amplification of growth factor receptor genes is closely related to the presence of polyploidy, irrespective of any different stemline DNA-ploidy mode. The time-course of oncogene amplification and kinds of genes amplified may differ between differentiated- and undifferentiated-type gastric cancers.