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Aberrant expression of cyclin E in low-risk node negative breast cancer
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
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2008 (English)In: Acta Oncologica, ISSN 0284-186X, Vol. 47, no 8, 1539-1545 p.Article in journal (Refereed) Published
Abstract [en]

Background. Cyclin E is a cell cycle regulatory protein which occurs in G1, peaks in late G1 and is degraded in early S-phase. Cyclin E overexpression appears to be an independent prognostic factor for overall survival in breast cancer. Material and Methods. Nuclear cyclin A is a reliable marker for S-and G2-phases. Consequently, aberrant expression of cyclin E can be detected by simultaneous immunostainings for cyclin A and cyclin E. Studies have shown that aberrant cyclin E might provide additional prognostic information compared to that of cyclin E alone. This study aimed to investigate cyclin E and aberrant cyclin E expression in low-risk node negative breast cancer. We compared women that died from their breast cancer (n=17) with women free from relapse>8 years after initial diagnosis (n=24). All women had stage I, low risk breast cancer. The groups were matched regarding tumour size, receptor status, adjuvant chemotherapy and tumour differentiation. Tumour samples were analysed regarding expression of cyclin A, cyclin E and double-stained tumour cells using immunoflourescence staining and digital microscopy. Results. No differences were seen regarding expression of cyclin E or aberrant cyclin E in cases compared to controls. Discussion. We conclude that neither cyclin E nor aberrant cyclin E is a prognostic factor in low-risk node negative breast cancer patients.

Place, publisher, year, edition, pages
2008. Vol. 47, no 8, 1539-1545 p.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-97140DOI: 10.1080/02841860701856581ISI: 000260227700010PubMedID: 18607847OAI: oai:DiVA.org:uu-97140DiVA: diva2:171945
Available from: 2008-04-29 Created: 2008-04-29 Last updated: 2009-06-25Bibliographically approved
In thesis
1. Cyclin A and cyclin E as prognostic factors in early breast cancer
Open this publication in new window or tab >>Cyclin A and cyclin E as prognostic factors in early breast cancer
2008 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Breast cancer is one of the most common malignancies in women. Due to early detection and the use of screening programs approximately 60% of all new cases lack lymph node involvement. Today, a substantial proportion of these women will be offered adjuvant systemic chemotherapy. However, better proliferation markers are needed to predict patient outcome and to avoid overtreatment.

Cyclin A, cyclin E and Ki-67 are all markers for proliferation and involved in the regulation of the cell cycle. Overexpression has been associated with disease recurrence in several studies, but the results have not been consistent. However, none of these studies has investigated aberrant expression of cyclin E (the expression of cyclin E during phases of the cell cycle other than late G1 and early S-phase). Studies have shown that aberrant cyclin E might provide additional prognostic information compared to cyclin E alone.

The aims of this thesis were 1.to investigate the prognostic value of cyclin A, cyclin E and aberrant cyclin E in early breast cancer. 2.to validate the tissue microarray (TMA) technique for cyclin A and 3.to define the most optimal cut-off values for cyclin A and Ki-67.

We found that the agreement of TMA and large section results was good with kappa values 0.62-0.75 and that the reproducibility of the two readers’ results was good or even very good, with kappa values 0.71 – 0.87.

The optimal cut-off value for cyclin A average was 8% and for cyclin A maximum value 11%. The corresponding values for Ki-67 were 15 and 22%.

Neither cyclin E nor aberrant cyclin E was a prognostic factor in low-risk node negative breast cancer patients.

Finally, we conclude that cyclin A is a prognostic factor in node negative breast cancer (univariate analysis average value OR=2.9 95% CI 1.8-4.6; maximum value OR=3.7 95% CI 2.3-5.9).

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2008. 57 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 343
Keyword
Oncology, breast cancer, chemotherapy, cyclin A, cyclin E, aberrant cyclin E, Ki-67, TMA, Onkologi
Identifiers
urn:nbn:se:uu:diva-8678 (URN)978-91-554-7181-1 (ISBN)
Public defence
2008-05-21, Wilandersalen, M-huset, Universitetssjukhuset Örebro, Örebro, 09:00
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Available from: 2008-04-29 Created: 2008-04-29Bibliographically approved

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