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Ki67 and cyclin A as prognostic factors in early breast cancer: What are the optimal cut-off values?
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
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2007 (English)In: Histopathology, ISSN 0309-0167, E-ISSN 1365-2559, Vol. 51, no 4, 491-498 p.Article in journal (Refereed) Published
Abstract [en]

AIMS: To find the optimal cut-off values for cyclin A and Ki67 in early breast cancer tumours and to evaluate their prognostic values. METHODS AND RESULTS: Tissue microarray (TMA) slides were constructed from 570 T1-4 N0-1 M0 breast cancer tumours. The TMA slides were stained for cyclin A and Ki67 using immunohistochemistry with commercial antibodies. To investigate the optimal cut-off values for cyclin A, Ki67 average and maximum values the material was split into two parts at cut-offs defined by dividing it into deciles. For each cut-off value the relative risk (RR) for metastasis-free survival (MFS) and overall survival (OS) was calculated comparing patients with high versus low cyclin A or Ki67 expression. When using a cut-off value around the seventh decile, cyclin A and Ki67 score correlated with the highest RR ratio for MFS in the chemotherapy-naïve subgroup. Among patients having received adjuvant chemotherapy, no statistically significant differences in MFS or OS were found. CONCLUSIONS: The optimal cut-off value for cyclin A average is 8% and for cyclin A maximum value 11%; for Ki67 the corresponding values are 15% and 22%. Additional studies are needed to verify these results.

Place, publisher, year, edition, pages
2007. Vol. 51, no 4, 491-498 p.
Keyword [en]
breast cancer, cut-off value, cyclin A, Ki67, tissue microarray
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-97139DOI: 10.1111/j.1365-2559.2007.02798.xISI: 000249661900008PubMedID: 17711446OAI: oai:DiVA.org:uu-97139DiVA: diva2:171944
Available from: 2008-04-29 Created: 2008-04-29 Last updated: 2017-12-14Bibliographically 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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Ahlin, CeciliaFjällskog, Marie-LouiseBlomqvist, Carl

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