Cyclin D1 and prognosis in human breast cancer

Abstract

We have used immunohistochemical staining to assess the expression of cyclin D I 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 for cyclin DI as compared with normal epithelium. Some tumours showed strong cytoplas-mic staining in the absence of nuclear staining, and around 25% of the tumours were judged to be negative for nuclear cyclin D I. Contrary to expectations, moderate/strong staining for cyclin D I was associated with improved relapse-free and overall survival relative to patients whose tumours stained weakly or negatively. Conversely, tumours that were considered negative for cyclin DI staining had an adverse prognosis, and the poor outcome was further accentuated if the tumours were also oestrogen receptor-negative. A possible explanation for our findings is that tumours in which cyclin D I levels are abnormally low may have sustained mutations in other genes, such as R 6 I and that it is this abnormality that has the more significant impact on survival from breast cancer. 8 1996 Wiley-Liss, Inc.

Abnormal Expression of Cell Cycle Regulatory Proteins in Ductal and Lobular Carcinomas of the Breast

“…Like two other studies (22,23), but unlike a third one (20), we found no association between cyclin D1 status and DNA ploidy. We were not able to study the association between positive estrogen receptor status and cyclin D1 overexpression, as has been documented by a number of other investigators (6,18,21,22).…”

“…Most previous reports also failed to demonstrate a correlation between cyclin D1 overexpression and size of the lesion, and no study has yet shown an association with axillary lymph node involvement (6, 18 -23). Likewise, the majority of published series failed to report a correlation with tumor grade (18 -22), although two groups reported a lower cyclin D1 positivity rate in high grade breast cancers (6,23). It is conceivable that the possible association with low grade may in part explain the favorable prognostic significance of cyclin D1 overexpression in breast cancer reported by some (6).…”

“…Likewise, the majority of published series failed to report a correlation with tumor grade (18 -22), although two groups reported a lower cyclin D1 positivity rate in high grade breast cancers (6,23). It is conceivable that the possible association with low grade may in part explain the favorable prognostic significance of cyclin D1 overexpression in breast cancer reported by some (6). However, the majority of published studies have found no survival difference between cyclin D1 negative and positive tumors.…”

“…In the present follow-up study, we wanted to test the hypothesis that in those tumors that had retained both pRB and p16, the G1 cell cycle checkpoint might be abrogated by abnormal expression of two other important genes, specifically cyclin D1 and p53. Cyclin D1 has been reported to be overexpressed in some 25 to 75% of breast cancers, and this may be associated with better survival (6). Accumulation of p53, which occurs in 10 to 60% of breast cancers, is usually taken as a surrogate marker of a mutation in the gene.…”

Lack of cyclin E immunoreactivity in non-malignant breast and association with proliferation in breast cancer

“…It contrasts with cyclin Dl, the other important G, cyclin, whose overexpression is known to correlate with the presence of oestrogen receptor (Gillet et al, 1996). A relationship was also found between p53 and cyclin E but this may be indirect as virtually all the carcinomas with p53 protein and cyclin E were poorly differentiated.…”