Gastric cancer development has been proposed to present a multistep process characterized by dysregulation of proliferation and differentiation and driven by an accumulation of genetic alterations in anatomic field repeatedly exposed to carcinogens. As a first part,of research for gastric carcinogenesis and prevention, we probed 30 early gastric cancers and their adjacent normal tissue including premalignant lesions for numerical chromosome aberrations by nonisotopic, in situ hybridization using chromosome specific centromeric DNA probe for chromosome 17, to visualize the accumulation of genetic alterations during gastric carcinogenesis and to determine the extent of the genetically altered field. The mean chromosome index(CI) increased as the tissue passed from normal adjacent gland(NG) to intestinal metaplasia(IM) to cancer(EGC) (l.06, 1.12, 1.26). Moreover, the frequency of cells with chromosome polysomy (cells with 3 or more chromosome copies) increased as same pattern (4.2%, 9.4%, 20.2%). All cases with EGC, 28/30 cases with IM, 15/30 cases with NG showed significant polysomies(i.e., polysomy frequency > 3% of total populations). As a second part of investigation, 30 cases of gastric adenoma tissue were probe with same centromeric chromosome probes for 5 and 17, to visualize the genetic alteration of isolated benign or premalignant gastric lesion. The mean CI were 1.16 and 1.17, respectively and the frequency of polysomy were 7.6% and 4.0%, respectively. These findings of progressive genetic changes as the the tumor develops support the concept of multistep carcinogenesis and field cancerization. Such genetic parameters could serve as biomarkers of intermediate end points for risk assessment of progression to malignancy or chemoprevention trials.
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