Analysis of the immunoreactivity of three anti-p53 antibodies and estimation of the relations between p53 status and MDM2 protein expression in ovarian carcinomas.

Background: The p53 growth suppressor is inactivated in human tumors by several distinct mechanisms, such as point mutations, binding to viral proteins and association with the MDM2 protein. Little is known about the expression of different immunologically distinct forms of p53 and MDM2 protein in human tumors and especially in ovarian carcinomas.

Materials And Methods: The overexpression of p53 and MDM2 oncoproteins was examined in a series of 46 ovarian carcinomas, taking into account the conventional pathological variables. The comparison of p53 and MDM2 expression in tissue sections and respective cyst and-or ascitic fluid cells was also performed. For the determination of the p53 expression the reactivity of three commonly used anti-p53 antibodies (DO7, PAb240, PAb1620), which detect immunologically distinct subclasses of p53, were analyzed in relation to the MDM2 status in individual patients.

Results: The detection of the p53 expression was clearly related to the antibody applied. DO7 antibody appears to be superior to both PAb240 and PAb1620 in immunohistochemical tests. Nuclear MDM2 protein overexpression was found in 17.4% of cases and usually it was associated with p53 accumulation. There was no significant correlation between p53 as well as MDM2 expression and histological subtypes, staging and grading parameters of carcinomas however p53 accumulation was detected more often in III/IV than in I/II FIGO stages.

Conclusion: In ovarian carcinomas significant inter- and intratumoral heterogeneity in p53 and MDM2 expression was identified and different MDM2/p53 phenotypes were revealed. The restriction of MDM2 overexpression to a small subset of neoplasms indicates that this oncoprotein plays a minor role in ovarian carcinogenesis.