P53 PROTEIN EXPRESSION IN BREAST CARCINOMAS - COMPARATIVE-STUDY WITH THE WILD-TYPE P53 INDUCED PROTEINS MDM2 AND P21 WAF1/

The aim was to investigate the pattern of expression of p53 protein an d two wild-type (wt) p53-induced proteins (mdm2 and p21/waf1), as an i ndirect way of assessing p53 gene status in breast carcinomas. Formali n-fixed paraffin embedded tissue from 102 cases of breast carcinomas c omprising mostly ductal carcinomas (88 cases) was stained by immunohis tochemistry for p53, mdm2 and p21/waf1 proteins. We found p53, mdm2 an d waf1/p21 protein expression in 33/102, 20/102 and 38/102 breast carc inomas, respectively. Parallel p53/mdm2 protein expression was found i n 9 cases. Five were also p21/waf1 positive. Discordant p53+/ mdm2-pro tein 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 carcino mas with wt p53 gene since mdm2 and p21 proteins are inducilbe by wt p 53 gene. In these cases p53 protein expression may be due to stabilisa tion to mdm2 protein. This could be important in the pathogenesis of t hese cases since mdm2 may deregulate in the p53-dependent growth suppr essive pathway. Discordant p53+/mdm2-/p21- protein expression may repr esent breast carcinomas with p53 gene mutations unable to activate exp ression 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. C ases with only mdm2 expression may represent tumours with mdm2 gene am plification or overexpression and cases with only p21 expression may r eflect p53-independent regulation of p21 protein.