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Overexpression of cyclin E protein is associated with specific mutation types in the p53 gene and poor survival in human breast cancer

På svenska

Author

  • T Lindahl
  • Göran Landberg
  • J Ahlgren
  • H Nordgren
  • T Norberg
  • S Klaar
  • L Holmberg
  • J Bergh

Summary, in English

Cyclin E is one of the key regulators of the G(1)/S transition in the cell cycle. Overexpression of cyclin E has been observed in several malignancies and is associated with high proliferation, aberrant expression of other cell cycle regulators and chromosomal instability in vitro. To explore potential associations between cyclin E deregulation and inactivation of the p53 tumor suppressor gene in human breast cancer, we investigated the immunohistochemical expression of cyclin E in paraffin embedded breast cancers from 270 women with known p53 status by cDNA based sequencing of the p53 gene. The breast cancers were divided into three subgroups according to the percentage of cyclin E-positive cells. One hundred and seventy-one patients (63%) had low cyclin E, 72 (27%) medium and 27 (10%) had high cyclin E content. Fifty-six percent (15/27) of the breast cancers with high cyclin E had p53 gene mutations, compared with 14% (24/171) of those with low cyclin E content (P < 0.0001). In p53 mutated breast cancers high cyclin E content was associated with insertions, deletions and nonsense point mutations in the p53 tumor suppressor gene, whereas low cyclin E was linked to p53 missense point mutations. We also observed statistically significant associations between a high cyclin E content and aneuploidy, high S phase, larger tumor size, estrogen receptor negativity, presence of axillary node metastases and high tumor grade. High cyclin E content was associated with poor overall survival in univariate and multivariate analysis (hazard ratio 2.4, 95% confidence interval 1.3-4.5). In summary, our findings demonstrate that overexpression of cyclin E is associated with an aggressive tumor phenotype and specific types of p53 mutations.

Department/s

Publishing year

2004

Language

English

Pages

375-380

Publication/Series

Carcinogenesis

Volume

25

Issue

3

Document type

Journal article

Publisher

Oxford University Press

Topic

  • Cancer and Oncology

Status

Published

Research group

  • Pathology, Malmö

ISBN/ISSN/Other

  • ISSN: 0143-3334