We have used immunohistochemical staining to assess the expression of
cyclin D1 in formalin-fixed sections of 345 breast carcinomas, dating
back 20 years. Clinical follow-up data were available on all patients.
Approximately 50% of the tumours showed excessive nuclear staining fo
r cyclin D1 as compared with normal epithelium. Some tumours showed st
rong cytoplasmic staining in the absence of nuclear staining, and arou
nd 25% of the tumours were judged to be negative for nuclear cyclin D1
. Contrary to expectations, moderate/strong staining for cyclin D1 was
associated with improved relapse-free and overall survival relative t
o patients whose tumours stained weakly or negatively. Conversely, tum
ours that were considered negative for cyclin D1 staining had an adver
se prognosis, and the poor outcome was further accentuated if the tumo
urs were also oestrogen receptor-negative. A possible explanation for
our findings is that tumours in which cyclin D1 levels are abnormally
low may have sustained mutations in other genes, such as RB1 and that
it is this abnormality that has the more significant impact on surviva
l from breast cancer. (C) 1996 Wiley-Liss, Inc.