p21/waf1/cip1 In gastric cancer: Associations with histopathological subtypes, lymphonodal metastasis, prognosis and p53 status

Background: Cyclins and cyclin-dependent kinases are determining factors of the cell cycle. In the present study, we investigated the role of p21 and p53 in the biology of gastric cancer, focusing on its influence on progress ion and prognosis (n = 195). Methods: P21 and p53 immunoreactivity was anal ysed immunohistochemically, applying monoclonal antibodies. The p53 status was comparatively evaluated by PCR-SSCP analysis of p53 mutations in select ed tumours. Results: Fifty-eight percent of the carcinomas were p21(+) in m ore than 5% of the cancer cell nuclei, whereas 19% exhibited a p21 immunore activity in more than 20% of the nuclei. On the other hand, p53 was over-ex pressed (in more than 50% of the nuclei) in about 45% of the specimens. P21 immunoreactivity in more than 5% of the nuclei was inversely related to th e pN as well as pTNM cancer stage, whereas only a strong p21 expression (in >20% of the nuclei) was correlated with a better survival probability in a univariate analysis. The p53 status was associated with lymphonodal metast asis, but not with prognostic data. In multivariate survival analyses, neit her p21 nor p53 emerged as independent prognostic factors. Compared with th e results of p53 mutation analysis by PCR-SSCP, p21 immunoreactivity was re duced in p53-mutated cases. Conclusions: These features show an association of p21 over-expression with certain clinico-pathological parameters of gas tric cancer. In this context, our data suggest that p21 immunoreactivity in more than 5% of the tumour cells has a predictive value for the course of adenocarcinoma of the stomach.