Prognostic Significance of DNA Image Cytometry in Libyan Breast Cancer

Abstract

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.

Proliferative Activity in Libyan Breast Cancer with Comparison to European and Central African Patients

“…In addition to the classic estimation of mitosis under microscope and then calculating the MAI and SMI, the proliferation activity can be evaluated by using new immunohistochemistry antibodies directed against different proliferation antigens, such as Ki-67 [17, 18], and proliferating cell nuclear antigen (PCNA) [19], or by analysis of the S-phase fraction using DNA cytometry [17, 20]. However, the S-phase fraction is weak method due to obvious intratumoral heterogeneity [21, 22].…”

Genome Instability Profiles Predict Disease Outcome in a Cohort of 4,003 Patients with Breast Cancer

“…The S-phase fraction was already subject of dozens of studies, analyzing its prognostic value in breast cancer. Assessed by means of image cytometry in breast cancer, it was shown to correlate with disease-specific survival as well as with larger tumor sizes and younger age at diagnosis (19,33). However, to our knowledge so far, no study analyzing the S-phase fraction by image cytometry on a comparably large and coherent cohort has been published.…”

“…Dozens of studies have been published to finally clarify the prognostic value of the DNA content measurements (14). However, due to (i) methodologic differences between the studies, such as different classification criteria, (ii) the inclusion of different cytometric parameters, and (iii) heterogeneous patient cohorts, contradictory results emerged (15)(16)(17)(18)(19).…”

DNA-cytometric characteristics of recurrent soft tissue sarcomas

“…В настоящее время исследуют способ прогнозирования течения опухолево го процесса при различных новообра зова ниях с использованием метода лазерной ДНК-проточной цитометрии [8][9][10]. В результате выявлено, что диплоидные опухоли имеют более благоприятное течение, чем анеуплоидные.…”

“…Данный метод позволяет определить плоидность опухолевых клеток, количество анеуплоидных клеток в опухоли, распределение по фазам клеточного цикла и индекс пролиферации. Сопоставление с клиническими данными, а также известными факторами прогноза позволяет рассматривать данный показатель как независимый прогностический признак [10,13]. Содержание ДНК в клетках и интенсивность клеточной пролиферации, темп деления опухолевых клеток являются важными составляющими, которые характеризуют агрессивность злокачественного процесса, биологические свойства опухоли и определяют течение заболевания [13].…”