These results indicate that (1) expression of a mutated p53 gene attenuates apoptotic cell death of gastric cancer, in accordance with the previous in vitro finding that p53 gene mutation provides a possible selective advantage for tumor cell proliferation, and (2) apoptosis is related not only to expression of p53 and the stage of the cell cycle, but also to p53-independent and cell cycle-independent events.
Moreover, analysis of both p53 status and DNA ploidy of tumors seems to provide very important information for evaluation of the prognosis of patients with advanced gastric cancer.
For evaluation of the prognostic relevance of p53 expression in gastric cancer, the immunohistochemical tissue status of 133 primary gastric cancer patients was investigated for p53 expression and the association between p53 tissue status and clinicopathological parameters was analyzed.
Mutation of the hMSH6 gene was observed in a subset of gastric cancers (4/30, 13.3%), but was not associated with P53 overexpression or APC gene mutation.
These data suggest that allelic deletion of the p53 gene in intestinal-type gastric carcinoma predicts the invasive potential of mucosal cancer, and that inactivation of the APC gene plays a role in the genetic tumorigenesis of both intestinal and diffuse types of gastric cancer.
DNA aneuploidy and overexpression of the p53 gene may play an important role in the early tumorigenesis of intestinal-type gastric cancer and in the late event of tumorigenesis of diffuse-type gastric cancer.
A study was carried out to assess whether p53 expression is related to tumour type, grade or pathological characteristics, or to prognosis, in gastric cancer.
There was a significant correlation between the immunoreaction of p53 and the depth of tumor invasion in gastric cancer, as well as between the decreased expression of DCC mRNA and nodal metastasis in colorectal cancer.
These results suggest that the immunohistochemical detection of p53 accumulation is a useful indicator of poor prognosis in the intestinal but not in the diffuse type of gastric cancer, and are indicative of distinct molecular pathways and pattern of progression in the two histotypes.
In contrast, GCs with MSS and MSI-L exhibit clinicopathologic features that are distinct from MSI-H tumors and have a higher frequency of TP53 mutations, suggesting that they may evolve through an entirely different pathway.
A substantial number of gastric cancers (31 of 105) showed positive p53 immunostaining without detectable mutations (p53-/IHC+), which suggested an accumulation of wild-type p53 protein, and also a significantly lower risk for metastasis.
To characterize phenotypic and genotypic changes in gastric cancer (GC), DNA copy number aberrations (CNAs) were assessed in 53 tumors using comparative genomic hybridization (CGH) and correlated with clinicopathologic characteristics and status of TP53 and replication error (RER).
These results suggest that DFMO induced MKN45 cell arrest at G(1) phase in a p53 independent manner, and Stat1 is, at least in part, involved in G(1) arrest.
The p53 and c-myc expression patterns indicate that EBV-infected gastric carcinomas are less likely to have a natural regression via apoptosis at an early stage and explain, in part, the resistance to treatment of late stage of gastric cancers.