p21WAF1 expression and endocrine response in breast cancer

✍ Scribed by McClelland, Richard A.; Gee, Julia M. W.; O'Sullivan, Louise; Barnes, Diana M.; Robertson, John F. R.; Ellis, Ian O.; Nicholson, Robert I.

• Publisher: John Wiley and Sons
• Year: 1999
• Tongue: English
• Weight: 231 KB
• Volume: 188
• Category: Article
• ISSN: 0022-3417
• DOI: 10.1002/(sici)1096-9896(199906)188:2<126::aid-path340>3.0.co;2-o

✦ Synopsis

An immunocytochemical assay for the p53-regulated protein product of the WAF1/Cip1 gene, p21 WAF1 (p21), was developed and applied to archival primary breast tumour material from 91 patients whose subsequent recurrent disease was treated with assessable courses of endocrine therapy. Nuclear localization of p21 protein was observed in 76 (82•4 per cent) cases. Status cut-offs were established and 29 (31•9 per cent) were deemed negative, 39 (42•9 per cent) weakly positive, and 23 (25•3 per cent) strongly positive. p21 status was inversely correlated with p53 protein (p=0•047) but did not relate to oestrogen receptor (ER) status, response to endocrine therapy, or time to further disease progression (TTP). Highly p21-positive patients had a significantly improved overall survival time (p=0•020). Co-assessment of p21 and p53 subgroups revealed p21+/p53 patients to have good survival characteristics, whilst p21 /p53+ patients did poorly (p=0•008). The p21 /p53 patients overall did intermediately well, but Ki67-defined cellular proliferation analysis of these revealed two subclasses: those with high proliferation and poor survival times resembling the p21 /p53+ phenotype, and those with less proliferative tumours with good survival, similar to the p21+/p53 group. The significance of these results is discussed in the light of recent research concerning the role of p21 and p53 in breast cancer aetiology.