Expression of Kirsten-ras p21 in gastric cancer correlates with tumor progression and is prognostic.

The purpose of this study was to determine the correlation between expression of ras oncoproteins and the tumor stage or outcome of patients with gastric carcinoma. After the specificity of each anti-ras monoclonal antibody was confirmed by protein immunoblot analysis, immunohistochemical assays for a common-ras antigen present in N-, Harvey- and Kirsten (K)-ras oncoproteins, as well as for K-ras specific antigen, were performed on paraffin-embedded carcinoma tissue from 110 patients who underwent curative resection. By Western blot analysis, there was more p21 in fresh cancer specimens than in normal specimens. K-ras expression distinguished advanced from early gastric carcinoma and correlated with depth of cancer invasion. Among the 110 patients, survival rates of those with carcinomas positive for the common-ras or K-ras antigens were significantly lower than of those with antigen-negative carcinomas (p < 0.05). In a multivariate analysis, nodal involvement (p = 0.002), serosal invasion (p = 0.012) and K-ras p21 expression (p = 0.044) were independently predictive of the recurrence. These results suggest that K-ras p21 is a useful marker of tumor progression and poor prognosis after curative resection.