Role of DNA aneuploidy, overexpression of p53 gene product, and cellular proliferation in the progression of gastric cancer

DNA aneuploidy, p53 overexpression, and high cell proliferation frequently occur in gastric cancer. However, little is known about the time of their a ppearance throughout cancer progression. Therefore, the objective of the pr esent study was to determine when such abnormalities occur during gastric c ancer progression. We classified the gastric cancers examined into intestin al (n = 65) and diffuse (n = 34) types. DNA ploidy was examined using flow cytometry and expression of MIB-1 and p53 immunoreactivity were studied usi ng the avidin-biotin complex method in three stages of gastric cancer (muco sal, submucosal, deeply invasive cancer, i.e., advanced cancer). The incide nce of DNA aneuploidy in intestinal-type mucosal cancers (15/27, 55.6%) was lower than that of submucosal invasive cancers (14/16, 87.5%) or advanced cancers (19/22, 86.4%), while a low incidence of DNA aneuploidy was observe d in each diffuse-type cancer group (mucosal, 1/12, 8.3%; submucosal invasi ve, 3/9, 33.3%; advanced, 8/14 57.1%). Although overexpression of the p53 g ene in intestinal-type cancer was found in early stage, that in diffuse-typ e cancer was observed in advanced stage. Among the intestinal-type mucosal cancers, the MIB-1 percent positive was higher in aneuploid tumors than dip loid ones. DNA aneuploidy and overexpression of the p53 gene may play an im portant role in the early tumorigenesis of intestinal-type gastric cancer a nd in the late event of tumorigenesis of diffuse-type gastric cancer. (C) 1 999 Wiley-Liss, Inc.