P21(WAF1) IMMUNOHISTOCHEMICAL EXPRESSION IN BREAST-CARCINOMA - CORRELATIONS WITH CLINICOPATHOLOGICAL DATA, ESTROGEN-RECEPTOR STATUS, MIB1 EXPRESSION, P53 GENE AND PROTEIN ALTERATIONS AND RELAPSE-FREE SURVIVAL

p21 protein (p21) inhibitor of cyclin-dependent kinases is a critical downstream effecter in the p53-specific pathway of growth control. p21 can also be induced by p53-independent pathways in relation to termin al differentiation. We investigated p21 immunoreactivity in normal bre ast and in 91 breast carcinomas [three in situ ductal carcinomas (DCIS ) with microinfiltration and 88 infiltrating carcinomas, 17 of which w ith an associated DCIS; 57 node negative and 34 node positive] with lo ng-term follow-up (median = 58 months). Seven additional breast carcin omas with known p53 gene mutations were investigated. In normal breast p21 expression mas seen in the nuclei of rare luminal cells of acinar structures, and in occasional myoepithelial cells. Poorly differentia ted DCIS showed high p21 expression, whereas well-differentiated DCIS tumours showed few p21-reactive cells. p21 was seen in 82 (90%) infilt rating tumours; staining was heterogeneous; the percentage of reactive nuclei ranged from 1% to 35%. High p21 expression (mere than 10% of r eactive cells) was seen in 24 (26%) casts, and was associated with hig h tumour grade (P = 0.032); no associations were seen with tumour size , metastases, oestrogen receptor status, MIBI expression and p53 expre ssion. p21 expression in cases with p53 gene mutations was low in six cases and high in one. High p21 expression was associated with short r elapse-free survival (P = 0.003).