Aims: To study the clinicopathological and prognostic value of cyclin D1
overexpression in patients with breast carcinoma. Methods and results:
Immunohistochemistry was performed on paraffin-embedded tissue specimens
from 290 invasive breast carcinomas to detect the proteins cyclin D1,
oestrogen receptor (ER), progesterone receptor (PR), p53, c-erbB2, and
topoisomerase IIa (topoIIa). Cyclin D1 staining was quantified using a
computerized image analysis method. Cyclin D1 overexpression
characterized smaller, ER-positive and PR-positive tumours (P = 0.017, P
< 0.0001, and P < 0.0001, respectively), of a lower histological and
nuclear grade (P = 0.011 and P < 0.0001, respectively), and with reduced
expression of topoIIa (P = 0.001) and p53 (P < 0.001). Cyclin D1 was
found to have an independent favourable impact on the overall survival
of both the unselected cohort of patients (P = 0.011) and of patients
with ER-negative and lymph node-positive tumours (P = 0.034 and P =
0.015, respectively). In triple-negative tumours, cyclin D1
overexpression was found to have independent favourable impacts on both
overall and relapse-free survival (P = 0.002 for both). Conclusions:
This is the first immunohistochemical study to dissociate the
advantageous prognostic effect of cyclin D1 overexpression from its
association with ER expression, and to provide evidence that cyclin D1
overexpression may be a marker of prolonged survival in patient
subgroups with aggressive phenotypes
