Clinical relevance of immunohistochemical expression of p53-targeted gene products mdm-2, p21 and bcl-2 in breast carcinoma

The present study was designed to investigate the clinical/prognostic relev ance of immunohistochemical expression of p53-targeted genes mdm-2, p21(WAF 1) and bcl-2 alone and in combination with p53 for the indirect assessment of p53 gene status in breast cancer. 141 archival breast carcinomas were im munostained, and the putative mutational status of the p53 gene was defined in 21 of them, as a control for immunohistochemistry, using the polymerase chain reaction single-strand conformational polymorphism (PCR-SSCP) analys is. Genetic changes of p53 correlated significantly with p53 protein overex pression (p = 0.01) but did not do so with any of the related molecules. Im munohistochemical p53 status was directly correlated with mdm-2 (p = 0.0001 ), p21 (p = 0.0004) and inversely with bcl-2 (p = 0.005) expression. bcl-2 proved to be an independent marker of prognosis, p,53 only in the group of node-positive carcinomas, whereas bcl-2(-)/p53(+) tumours revealed the wors t prognosis. Mdm-2 and p21 expression was of prognostic significance neithe r alone nor in combination. We conclude that the detection of downstream re gulators of p53 does not increase the efficacy of immunohistochemistry in a ssessing the functional status of p53 in breast cancer; however, their comb ined analysis may help to select subgroups of patients at the extremes of r isk for recurrence, or those with greater chances for survival.