ABSENCE OF RAS GENE-MUTATIONS IN EARLY GASTRIC CARCINOMAS

The aims of this study were to assess the prevalence and type of activ ating point mutations at codons 12, 13, and 61 of the Ki-, Ha-, and N- ras genes in a series of early gastric carcinomas in white patients an d to correlate these ras gene mutations, if any, with the histological type (Lauren classification), the type of growth pattern, and with th e Helicobacter pylori status. Haematoxylin and eosin and Giemsa staine d sections from 45 formalin fixed, paraffin wax embedded early gastric carcinomas were used to assess the Lauren type, the type of growth pa ttern, and the antral H pylori status. DNA was extracted according to standard procedures. Mutations at codon 12 of the Ki-ras gene were exa mined with a polymerase chain reaction based restriction fragment leng th polymorphism (PCR-RFLP) method and dot blot hybridisation with alle le-specific P-32-labelled oligodeoxynucleotide (ASO) probes. All other ras genes were analysed with specific PCR amplification and dot blot hybridisation with ASO probes. Mutations were detected by overnight au toradiography at -70 degrees C. Some 20 Netherlands intestinal-type an d 25 diffuse-type early gastric carcinomas were seen. According to gro wth pattern, there were 24 small mucosal type early gastric carcinomas , five superficial spreading type early gastric carcinomas, and 16 pen etrating type early gastric carcinomas (four penetrating A type, 12 pe netrating B type). H pylori was found in the antral mucosa of 28 early gastric carcinomas (62%). Activating ras gene mutations were not foun d. It was discovered that activating point mutations at codons 12, 13, and 61 of the Ki-, Ha-, and N-ras genes do not play a part in the dev elopment of early gastric carcinomas in white subjects, irrespective o f Lauren type. Moreover, differences in biological behaviour between e arly carcinomas with different types of growth pattern are not related to these ras gene mutations. Finally, H pylori positive and H pylori negative gastric carcinomas cannot be discriminated on the basis of ra s gene mutational analysis.