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

Yildirim-Assaf, Selma; Coumbos, A.; Hopfenmüller, Werner; Foss, Hans‐Dieter; Stein, Harald; Kühn, W

doi:10.1136/jcp.2005.035550

Cited by 21 publications

(13 citation statements)

References 49 publications

(19 reference statements)

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“…Our study revealed that aneuploid tumors and tumors with high SPF correlated significantly with shorter survival time. Also the breast cancer patients with aneuploid cells below the cutoff value showed a significantly longer overall survival than those with aneuploid cells above this value, a finding that is in agreement with the results of other studies [7,16,17]. …”

Section: Discussionsupporting

confidence: 82%

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Prognostic Significance of DNA Image Cytometry in Libyan Breast Cancer

et al. 2012

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Background: We evaluated the relation of nuclear DNA content and clinicopathological features and prognosis in primary breast cancer of female Libyan patients with variable stage and grade and different treatment regimes. Patients and Methods: Histological samples from 104 patients of breast carcinoma were retrospectively studied by computerized nuclear DNA cytometry. Isolated nuclei from paraffin sections were stained with Feulgen stain and DNA was measured using a computer-assisted image analysis cytometry system. In each case, 200 nuclei were measured and the DNA histograms, S phase fraction (SPF) and number of cells above 5c and 9c were determined. We applied different approaches in the analysis of DNA to compare the DNA histograms with different clinicopathological features and survival. Results: The mean of DNA ploidy mode for all tumors was 3.43; 82.7% of tumors were aneuploid and 17.3% were diploid. The median SPF was 3.5% for DNA diploid and 13.5% for DNA aneuploid tumors. DNA aneuploid tumors and high SPF were associated with advanced stage, distant metastasis, high histological grade and lymph node involvement. The SPF was also associated with large tumor size and with younger patients (<50 years). In the overall population (median follow-up 51 months), patients with aneuploid DNA histograms and high SPF values had shorter survival times than those with diploid DNA histograms and low SPF values (p = 0.001, p < 0.0001, respectively). Also, short survival was associated with a multiploid DNA histogram and with DNA aneuploid cells ≥5 cells (p < 0.0001, p = 0.001, respectively). In a Cox multivariate analysis, DNA ploidy (p = 0.010), age (p = 0.038) and clinical stage (p = 0.001) were independent predictors of overall survival, and DNA ploidy (p = 0.018) and clinical stage (p = 0.001) also proved to be independent predictors of disease-specific survival. The SPF cutoff point of 11% might be applied to separate patients into good and poor prognosis groups. Conclusions: DNA image cytometry with careful analysis of the histograms may provide valuable prognostic information in Libyan breast cancer, with potential clinical implications in patient management, particularly in predicting the patients at high risk for metastasis and recurrence who should be considered as candidates for combined adjuvant therapy.

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Section: Discussionsupporting

confidence: 82%

“…Our study, in fact, is a natural response to the recommendations of different studies [3,4] focusing on breast cancer in the MENA region. To our knowledge, this is the first study to investigate the prognostic value of nuclear DNA content in Libyan breast cancer and compare the results with other countries [5,6,7]. …”

Section: Introductionmentioning

confidence: 99%

Prognostic Significance of DNA Image Cytometry in Libyan Breast Cancer

et al. 2012

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“…Such aneuploidy-associated protein expression patterns could reveal novel diagnostic and therapeutic targets. Our general conclusions were supported by the findings of Sinicrope et al, Bosari et al, and Yildirim-Assaf et al showing that patients with aneuploid tumors had a worse outcome compared to patients with euploid tumors (Sinicrope, Rego, Halling, et al 2006;Bosari et al 1992;Yildirim-Assaf et al 2007). Despite this clear demonstration of an association of aneuploidy and outcome the American Society of Clinical Oncology (ASCO) does not recommend ploidy assessment in clinical routine.…”

Section: Discussionsupporting

confidence: 79%

Aneuploidy and Epithelial Cancers: The Impact of Aneuploidy on the Genesis, Progression and Prognosis of Colorectal and Breast Carcinomas

Habermann¹,

Auer²,

Upender³

et al. 2012

Aneuploidy in Health and Disease

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“…Several studies observed the prognostic value of SPF in breast cancer 19-21. High SPF was significantly associated with advanced stage, large pathological tumor size, lymph node involvement, poor differentiation of tumors and low survival in the patients with breast carcinoma 10, 11.…”

Section: Introductionmentioning

confidence: 99%

Prognostic Value of Proliferation Markers: Immunohistochemical Ki-67 Expression and Cytometric S-Phase Fraction of Women with Breast Cancer in Libya

Ermiah¹,

Buhmeida²,

Abdalla³

et al. 2012

J. Cancer

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Background: We evaluated the association of the immunohistochemical Ki-67 expression, and S-phase fraction with clinicopathological variables and patient outcome.Patients and methods: Histological samples from 100 primary Libyan breast carcinoma patients were retrospectively studied with monoclonal antibody to Ki-67. S-phase fraction was determined by DNA image cytometry.Results: The median Ki-67 percentage for all tumors was 27.5%, ranging from 1 to 80% and the median S-phase fraction (SPF) was 11%, ranging from 0 to 62 %. Tumors with high Ki-67 expression were found in 76% of patients and with high SPF values in 56%. Ki-67 expression was more frequent in tumors with high SPF than low SPF. High Ki-67 and high SPF were associated with advanced stages, poor differentiation of tumors, positive lymph nodes, and distant metastasis. The Ki-67 was associated with hormone receptor negative tumors. The SPF was higher in young patients (<50 years) than in older patients. In the overall population (median follow-up 49 months), patients with high Ki-67 and high SPF had shorter survival time and predicted recurrence than patients with low Ki-67 and low SPF. In a Cox multivariate analysis, high SPF (p= 0.007), hormonal status (p= 0.001) and clinical stage (p=0.005) were independent predictors of disease-specific survival. The Ki-67 (p=0.065) in borderline significance proved to be independent predictor of disease-free survival. The SPF showed more statistically significance with a high grade of malignancy and survival time than Ki-67.Conclusions: The SPF value is useful cell proliferation marker to assess tumor prognosis. These markers may reflect the aggressive behavior of Libyan breast cancer and predict of the recurrence. It is therefore important to take these markers into consideration to select a high risk subgroup of the patients for intensive treatment.

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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

Cited by 21 publications

References 49 publications

Prognostic Significance of DNA Image Cytometry in Libyan Breast Cancer

Prognostic Significance of DNA Image Cytometry in Libyan Breast Cancer

Aneuploidy and Epithelial Cancers: The Impact of Aneuploidy on the Genesis, Progression and Prognosis of Colorectal and Breast Carcinomas

Prognostic Value of Proliferation Markers: Immunohistochemical Ki-67 Expression and Cytometric S-Phase Fraction of Women with Breast Cancer in Libya

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