ABSENCE OF P21 EXPRESSION IS ASSOCIATED WITH ABNORMAL P53 IN HUMAN BREAST CARCINOMAS

The p53 tumour-suppressor gene is important in the regulation of cell growth and apoptosis, and loss of functional wild-type activity may be associated with tumour formation and resistance to therapy. Different iation of functionally normal wild-type protein from mutant or abnorma l protein remains difficult using either immunohistochemical assays or mutational DNA sequencing, p21(WAF1/CIP1) (p21) is induced by wild ty pe p53 and plays an important role in promoting cell cycle arrest. To test the hypothesis that p21 protein expression may act as a downstrea m marker of tumours from patients with locally advanced breast cancer before treatment with doxorubicin, pretreatment p53 status had been ch aracterized in 63 tumours by p53 protein immunostaining and DNA mutati onal analysis. There was a significant association between immunostain ing for p53 and the presence of p53 mutations (P = 0.01). Of 56 patien ts available for determination of p21, 31 (55%) expressed p21 protein. Twenty-eight out of 31 patients (90%) positive for p21 had low negati ve p53 protein expression, whereas only 3 of 13 patients (23%) with hi gh p53 expressed p21 (P = 0.009), No association was seen between p21 protein expression and p53 mutations (P = 0.24). The combination of p5 3 and p21 immunostaining results improved the specificity of the immun ostaining but at a cost of significant reduction in sensitivity. Immun ohistochemical assessment of p21 protein expression is inversely assoc iated with abnormal p53 protein in human breast cancer, The detection of p21 protein expression in combination with p53 protein expression d id not improve the ability of immunohistochemistry (IHC) to differenti ate between normal and mutant p53 protein.