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Journal of Clinical Pathology 2007;60:649-655; doi:10.1136/jcp.2005.035550
Copyright © 2007 by the BMJ Publishing Group Ltd & Association of Clinical Pathologists.

ORIGINAL ARTICLE

The prognostic significance of determining DNA content in breast cancer by DNA image cytometry: the role of high grade aneuploidy in node negative breast cancer

Selma Yildirim-Assaf1, Alexandra Coumbos1, Werner Hopfenmüller2, Hans-Dieter Foss3, Harald Stein3 and Wolfgang Kühn1

1 Department of Gynecology and Obstetrics, Charité-Campus Benjamin Franklin, Universitätsmedizin Berlin, Berlin, Germany
2 Institute of Medical Informatics, Biometrics and Clinical Epidemiology, Charité-Campus Benjamin Franklin, Universitätsmedizin Berlin, Berlin, Germany
3 Institute of Pathology, Charité-Campus Benjamin Franklin, Universitätsmedizin Berlin, Berlin, Germany

Correspondence to:
Correspondence to:
Dr Selma Yildirim-Assaf
Department of Gynecology and Obstetrics, Charité-Universitätsmedizin Berlin, Hindenburgdamm 30, 12200 Berlin, Germany; selma.yildirim-assaf{at}charite.de

Aim: To investigate the role of DNA aneuploidy, particularly in patients with node negative breast cancer, in order to identify the different risk profiles within the pool of heterogeneous breast cancers.

Methods: Imprint smears from 370 breast carcinomas were Feulgen-stained and measured by DNA image analysis. DNA aneuploidy was graded by the amount of aneuploid cells (DNA content >5c) and highly aneuploid cells (DNA content >9c) in a breast tumour population. These results were correlated to the clinical long-term follow-up. A statistical cut-off value of >10 aneuploid cells (>5c) and of >1 highly aneuploid cell (>9c) was evaluated as significant for disease-free survival (DFS) and overall survival (OS).

Results: Subgroups among patients with breast cancer with aneuploid cells below the cut-off value showed a significantly longer DFS and OS than those with aneuploid cells above this value. Patients with node negative breast cancer with >10 aneuploid cells (>5c) and >1 highly aneuploid cell (>9c) showed an unfavourable prognosis similar to patients with node positive breast cancer with <10 aneuploid cells (>5c) and <1 highly aneuploid tumour cell (>9c) in DFS and OS.

Conclusion: Nuclear DNA content, as an objective marker of tumour aggressiveness, provides prognostic information in patients with both node negative and node positive breast cancer. Based on DNA aneuploidy, the clinically inhomogeneous group of patients with node negative breast cancer can be stratified into low-risk and high-risk subgroups. Therefore, DNA ploidy analysis may identify high-risk patients with lymph node negative breast cancer who might benefit from additional adjuvant therapy.

Abbreviations: DFS, disease-free survival; OS, overall survival

Keywords: DNA aneuploidy; 5c- and 9c-exceeding rate; DNA image cytometry; Auer classification, breast cancer; prognosis


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