Nuclear accumulation of p53 protein in gastric cancer strongly correlates with enlargement of nuclear area of cancer cells

The nuclear area (NA) of cancer cells have been reported to be a useful prognostic indicator in various tumors. However, this image analysis of cancer nucleus has only rarely been applied to gastric adenocarcinoma. Moreover, it remains to be shown what types of biological factors influence this nuclear feature. In this study, we analyzed the area of cancer nuclei in tumors from 97 patients with advanced gastric cancer (t3, n0, stage II) by using hematoxylin and eosin stained slides with a computer-assisted image-analysis system. The morphometric data were compared with clinicopathological and biological status of the tumors. The mean NA of 50 tumors with venous invasion (50 microm2) was significantly larger than that of 47 tumors without venous invasion (38 microm2, p<0.0001). There was a significant correlation between the NAs of cancer cells and the p53 labeling indices of tumors (p=0.0012) and Ki-67 labeling indices of tumors (p=0.0324). However, no significant correlation was detected between the NAs of cancer cells and other factors, such as, tumor size, DNA ploidy pattern, expression of vascular endothelial growth factor (VEGF), or microvessel density of tumors. The five-year survival rate of 49 patients with large nuclear area (NA > or =41 microm2, 63%) was significantly lower than that of 48 patients with small nuclear area (NA <41 microm2, 78%, p=0.043). Data from computerized morphometry are objective and can be obtained rapidly by conventional microscopic analysis. The NA of cancer cells in advanced gastric cancer appears to predict the ability to invade the microvessels in the gastric wall. This nuclear morphological feature strongly correlated with p53 accumulation in the nuclei of gastric adenocarcinoma.