P21/WAF1/Cip1 expression in invasive ductal breast carcinoma: relationshipto p53, proliferation rate, and survival at 5 years

The p21/WAF1/Cip1 antibody, DCS-60, was characterized by means of immunoblo tting and immunofluorescence on a variety of human breast cancer cell lines . Heterogeneous staining of nuclei was observed with strong staining of cel ls in early G(1)-p21/WAF1/Cip1 expression in invasive ductal, not otherwise specified breast carcinomas was determined using immunohistochemistry with this antibody and computerized image analysis. Two hundred and twenty-two tumors, including 130 from patients with no axillary node involvement, were examined. p21-positive tumor cell nuclei were found in 30% of the breast c arcinomas. The percentage of tumor cell nuclei that were positive ranged fr om less than 1% to greater than 10%. In the whole cohort of patients, p21 e xpression was significantly associated with a low histological grade. In th e node-negative group, there was a significant negative correlation between p21 positivity and a high (> 10%) MIB-1 score. The mean MIB-1 score was si gnificantly lower in p21-positive, tumors in the whole cohort of patients ( P=0.03) and in the node-negative group (P=0.02). No association was found b etween p21 expression and overall survival at 5 years. With respect to p21/ p53 phenotype, the significant difference in survival was noted only for th e group of patients treated with adjuvant chemotherapy. The p21- p53+ pheno type had the worst survival (58% surviving 5 years), while the p21+ p53- ph enotype had good survival (83% surviving 5 years; P <0.05). The results see m to suggest a correlation between p21/p53 phenotype and response to adjuva nt chemotherapy.