EXPRESSION OF P53, MDM2, P21 WAF1 AND BCL-2 PROTEINS IN THYMOMAS/

We have investigated the immunohistochemical expression of p53, mdm2, p21/waf1 and bcl-2 proteins in 31 thymic epithelial tumours comprising ave medullary thymomas (MDT), four mixed thymomas (MT), 12 cortical t hymomas (CT), eight predominately cortical thymomas (PCT) and two well -differentiated thymic carcinomas (WDTC). We have found p53, mdm2, p21 and bcl-2 protein expression in 25/31, 8/31, 5/31 and 10/31 thymic ep ithelial tumours, respectively Coexpression of p53 and mdm2 proteins w as found in eight cases (three CT, four PCT and one WDTC). Five of the m were also p21 positive and three p21 negative, Discordant p53+/mdm2- /p21- protein expression was found in 19 cases (three MDT three MT, ni ne CT, three PCT and one WDTC). Mdm2 and p21 proteins were not express ed in the absence of p53 protein, Coexpression of bcl-2 and p53 protei ns was found in seven cases (three MDT, three MT and one WDTC). Eighte en cases were p53+/bcl-2- (10 CT, seven PCT and one WDTC) and three ca ses (two MDT and one MT) were bcl-2+/p53-. Our findings indicate that in thymomas, p53 expression is more frequently associated with cortica l histotypes while bcl-2 expression is strongly associated with medull ary and mixed histotypes. In addition, there is an inverse correlation between p53 and bcl-2 protein expression in thymomas. Coexpression of p53/mdm2/p21 proteins may reflect thymomas with wild-type (wt), p53 g ene since mdm2 and p21 proteins are inducible by wt p53 gene. However, in view of previous findings that p53 mutation is an early event in t hymomas, the possibility of p53 gene mutation with p53-independent mdm 2 and p21 expression should be considered in these cases. Discordant p 53+/mdm2-/p21- protein expression may represent thymomas with p53 gene mutations unable to activate expression of mdm2 and p21 proteins.