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Reliability of cyclin A assessment on tissue microarrays in breast cancer compared to conventional histological slides
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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2006 (English)In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 94, no 11, 1697-1702 p.Article in journal (Refereed) Published
Description
Abstract [en]

Cyclin A has in some studies been associated with poor breast cancer survival, although all studies have not confirmed this. Its prognostic significance in breast cancer needs evaluation in larger studies. Tissue microarray (TMA) technique allows a simultaneous analysis of large amount of tumours on a single microscopic slide. This makes a rapid screening of molecular markers in large amount of tumours possible. Because only a small tissue sample of each tumour is punched on an array, the question has arisen about the representativeness of TMA when studying markers that are expressed in only a small proportion of cells. For this reason, we wanted to compare cyclin A expression on TMA and on traditional large sections. Two breast cancer TMAs were constructed of 200 breast tumours diagnosed between 1997-1998. TMA slides and traditional large section slides of these 200 tumours were stained with cyclin A antibody and analysed by two independent readers. The reproducibility of the two readers' results was good or even very good, with kappa values 0.71-0.87. The agreement of TMA and large section results was good with kappa value 0.62-0.75. Cyclin A overexpression was significantly (P<0.001) associated with oestrogen receptor and progesterone receptor negativity and high grade both on TMA and large sections. Cyclin A overexpression was significantly associated with poor metastasis-free survival both on TMA and large sections. The relative risks for metastasis were similar on TMA and large sections. This study suggests that TMA technique could be useful to study histological correlations and prognostic significance of cyclin A on breast cancer on a large scale.

Place, publisher, year, edition, pages
2006. Vol. 94, no 11, 1697-1702 p.
Keyword [en]
breast cancer, cyclin A, tissue microarray, Biopsy/methods, Breast Neoplasms/*pathology/radiotherapy, Cyclin A/analysis/*genetics, Female, Humans, Reproducibility of Results, Tissue Array Analysis/*methods
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-97138DOI: 10.1038/sj.bjc.6603147PubMedID: 16670718OAI: oai:DiVA.org:uu-97138DiVA: diva2:171943
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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