Skip to main content
  • Paper Report
  • Published:

Cyclin D1in breast cancer is not associated with Ki67 but with ER


D-type cyclins are implicated in cell cycle regulation. The cyclin D1 gene is amplified in 15-20% of breast cancers while the protein is overexpressed in 50% of these cancers (see Additional information [1]). Overexpression of cyclin D1 has been linked with oestrogen receptor (ER)a, because it can stimulate transcriptional functions in the absence of oestrogen (see Additional information [2]). A negative association in normal breast has been reported for ERa and Ki67 (a proliferation marker), although this relationship changes in many precancerous and ER-positive cancers. Therefore, the aim of the study was to investigate the interaction between cyclin D1, ER and Ki67 in normal and malignant breast material.

Significant findings

The mean percentage of ER-positive cells in normal breast tissues was 20%. Approximately 50% of the cyclin-D1-positive cells coexpressed ER. However, cyclin-D1-positive cells were detected in 70% of ER-positive invasive ductal carcinomas (IDCs) and in 30% of ER-negative IDCs. In normal breast tissues, Ki67-positive cells accounted for 3% of the epithelial cells while only 0.3% contained cyclin D1. In benign breast lesions no clear outcome was detected for cyclin D1 and Ki67. Invasive cancers showed a higher percentage of Ki67-positive cells than normal tissue and this was significantly higher in ER-negative than in ER-positive carcinomas. Overall a positive correlation between cyclin D1 and ER-positive cells was detected in normal and cancerous breast tissues, while a negative association was detected between cyclin D1 and Ki67.


Cyclin D1 overexpression has been associated with low grade ER-positive breast cancers (see Additional information [3]). In this study no cyclin D1 positivity was detected in ER-negative breast cancers that contained a high percentage of Ki67-positive cells. A number of studies indicate that cyclin D1 overexpression increases progressively from normal breast epithelium to atypical ductal hyperplasia (ADH), to ductal carcinoma in situ (DCIS) and to invasive cancers respectively (see Additional information [4,5]). The authors observed that cyclin D1 was higher within in situ proliferations than in normal breasts, while in ADH cases similar values to those measured in ER-positive DCIS were seen. Therefore, they concluded that cyclin D1 was not the ideal marker for separating benign from malignant breast lesions. Future studies should investigate further the interactions of cyclin D1 and Ki67 expression in larger cohorts and include other histological carcinoma types.


Dual immunofluorescence immunohistochemistry

Additional information

  1. 1.

    Barnes DM: Cyclin D1 in mammary carcinoma. J Pathol 1998, 181:267-269 (PubMed abstract).

  1. 2.

    Zwijsen RML, Wientjens E, Klompmaker R, van der Sman J, Bernards R, Michalides RJAM: CDK-independent activation of oestrogen receptor by cyclin D1. Cell 1997, 88:405-415 (PubMed abstract).

  1. 3.

    van Diest PJ, Michalides RJ, Jannink L, van der Valk P, Peterse HL, de Jong JS, Meijer CJ, Baak JP: Cyclin D1 expression in invasive breast cancer. Correlations and prognostic value. Am J Pathol 1997, 150:705-711 (PubMed abstract).

  1. 4.

    Alle KM, Henshall SM, Field AS, Sutherland RL: Cyclin D1 protein is overexpressed in hyperplasia and intraductal carcinoma of the breast. Clin Cancer Res 1998, 4:847-854 (PubMed abstract).

  1. 5.

    Zhu XL, Hartwick W, Rohan T, Kandel R: Cyclin D1 gene amplification and protein expression in benign breast disease and breast carcinoma. Mod Pathol 1998, 11:1082-1088 (PubMed abstract).


  1. Shoker BS, Jarvis C, Davies MPA, Iqbal M, Sibson DR, Sloane JP: Immunodetectable cyclin D1is associated with oestrogen receptor but not Ki67 in normal, cancer and precancerous breast lesions. Br J Cancer . 2001, 84: 1064-1068.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations


Rights and permissions

Reprints and permissions

About this article

Cite this article

Skliris, G. Cyclin D1in breast cancer is not associated with Ki67 but with ER . Breast Cancer Res 3, 68466 (2001).

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: