Out of 11 patients with gastric cancer, 3 were treated with chemotherapeutic drugs before resection; 5 of 13 patients with colorectal cancer had 30 Gy radiation prior to surgery. p53 mutations were detected in 4 cases of gastric cancer (36.4%) and in 6 cases of colorectal cancer (46.2%) by immunohistochemical staining.
This allows the cell to repair its DNA or, if the damage is irreversible, to elicit apoptotic cell death. p53 mutations are seen in many human tumors including gastric carcinoma.
The role of normal and mutated p53 proteins has been studied in depth in a variety of cell types, and p53 alterations have been extensively analysed in many human tumors, including gastric cancer.
Mutations of the p53 gene were investigated in 80 surgical specimens of primary gastric cancer by polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) analysis.
In multivariate analysis adjusted for the other histopathological parameters, p53 gene mutation but not immunohistochemically-detected p53 protein accumulation was an independent prognostic indicator of poor survival in gastric carcinoma.
The expression of p21 and p53 protein was analyzed by immunohistochemistry in 93 patients with advanced gastric carcinoma with serosal invasion and lymph node metastasis.
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.
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.
Overexpression of p53 was more frequent in early intestinal than early diffuse GC and was noted in the stage progression of diffuse but not intestinal GC.
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.
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.
Similarly, p53 overexpression was more frequently found in the intestinal type (19/32, 59.4%) and the advanced stage (24/45, 53.3%) than in the diffuse type (8/28, 28.6%) and the early stage (3/15, 20.0%) of GC (P<0.05).
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.
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.
Epstein-Barr virus and gastric carcinoma in Western patients: comparison of pathological parameters and p53 expression in EBV-positive and negative tumours.