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p53 protein expression in breast carcinomas. Comparative study with the wild type p53 induced proteins mdm2 and p21/waf1 (Journal article)

Giannikaki, E./ Kouvidou, C./ Tzardi, M./ Stefanaki, K./ Koutsoubi, K./ Gregoriou, M./ Zois, E./ Kakolyris, S./ Mavroudi, C./ Delides, G./ Georgoulias, V./ Kanavaros, P.

The aim was to investigate the pattern of expression of p53 protein and two wild-type (wt) p53-induced proteins (mdm2 and p21/waf1), as an indirect way of assessing p53 gene status in breast carcinomas. Formalin-fixed paraffin embedded tissue from 102 cases of breast carcinomas comprising mostly ductal carcinomas (88 cases) was stained by immunohistochemistry for p53, mdm2 and p21/waf1 proteins. We found p53, mdm2 and waf1/p21 protein expression in 33/102, 20/102 and 38/102 breast carcinomas, respectively. Parallel p53/mdm2 protein expression was found in 9 cases. Five were also p21/waf1 positive. Discordant p53+/ mdm2-protein expression was found in 24 cases. Nine were p21/waf1 positive and the remaining fifteen were p21/waf1 negative. The patterns mdm2+/p53-/p21- and p21+/p53-(+)/mdm2- were found in 6 and 20 cases, respectively. Parallel p53/mdm2/p21 protein expression may represent breast carcinomas with wt p53 gene since mdm2 and p21 proteins are inducible by wt p53 gene. In these cases p53 protein expression may be due to stabilisation to mdm2 protein. This could be important in the pathogenesis of these cases since mdm2 may deregulate the p53-dependent growth suppressive pathway. Discordant p53+/mdm2-/p21- protein expression may represent breast carcinomas with p53 gene mutations unable to activate expression of mdm2 and p21 proteins. Breast carcinomas with p53+/mdm2/p21+ protein expression may have either wt p53 with deregulated mdm2 gene expression or mutated p53 gene with p53-independent p21 expression. Cases with only mdm2 expression may represent tumours with mdm2 gene amplification or overexpression and cases with only p21 expression may reflect p53-independent regulation of p21 protein.