Expression of the p53 homologues p63 and p73 in multiple simultaneous gastric cancer

The tumour-suppressor protein p53 has recently been shown to belong to a fa mily that includes two structurally related proteins, p63 and p73. This stu dy investigated the status of p53 and its two homologues in multiple simult aneous gastric carcinomas. Expression and mutation of p-53, p73 and p63 inc luding the two major isotypes TAp63 and Delta Np63, were examined by direct DNA-sequencing, in situ hybridization, western blotting and immunohistoche mistry in 68 gastric carcinomas of 32 patients. The results obtained were c orrelated with pathohistological stage (according to UICC16) and several ot her histopathological factors and finally with patient survival. p53 mutati ons were detected in 23/68 carcinomas (34%) from 18 patients with a discord ant mutation pattern. Independently of p53 mutation status, p73 transcripts and protein expression were found in 33/68 carcinomas from 24 patients. p6 3 positivity was found in 21 patients; 25 out of 68 tumours expressed p63. The number of cells containing p63 and their distribution depend on the deg ree of tumour differentiation. High grade carcinomas of the diffuse type ex hibited a significantly higher p63 expression. In intestinal metaplasia and atrophic gastritis, an increase of TAp63 and Delta Np63 staining was also observed. Specific mutations of p73 or p63 causing amino acid substitutions were not identified. Neither p53, p73 nor p63 were related to prognosis. p 73 and p63 have rarely been found to be mutated in gastric carcinomas, but both proteins were expressed in only a subset of tumours. The status of the se p53 homologues was discordant in all patients with multiple simultaneous gastric carcinomas. The increased expression of p63 (TAp63 and Delta Np63) in less well differentiated gastric carcinomas may indicate that p63 can a ct to promote neoplastic growth in the gastric epithelium. Copyright, (C) 2 001 John Wiley & Sons, Ltd.