Flow Cytometry Dna Ploidy and Number of Cell Populations in the Primary Breast Cancer and Their Correlation to the Prognosis (original) (raw)
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Flow cytometric DNA ploidy defines patients with poor prognosis in node-negative breast cancer
International Journal of Cancer, 2007
Flow cytometric DNA analysis was performed on fine-needle aspirates from frozen tumour biopsies from 42 I node-negative, non-adjwantly-treated breast-cancer patients with a median observation time of 6.75 years. Among premenopausal patients (n = 175), those having at least one DNA "hypoploid" subpopulation defined as DNA index (DI) ~0. 9 6 or 1.44 S DI < 1.92 (n = 81) were characterized by early recurrences (logrank p = 0.05, Wilcoxon p = 0.007), poor overall survival (0s) (p < 0.001) and poor survival after recurrence (p < 0.001). In the postmenopausal group (n = 246). there were no significant differences among 7 different DI classes regarding either recurrence-free survival (RFS) or 0s. S-phase fraction (SPF), divided into quartiles, predicted 0 s in premenopausal patients only (p = 0.02). Conventional multivariate Cox analysis of 0 s in the premenopausal group revealed hypoploidy to be the only independent prognostic factor involving a relative risk (RR) of 22.8. Age 5 40 years was of marginal significance, whereas SPF, histological grade (WHO), oestmgen and progesterone receptor (PgR) content, tumour size and number of lymph nodes removed were excluded from the model. Application of the conventional Cox model to the premenopausal group regarding RFS was found inappropriate due to lack of proportionality of the hazards of hypoploidy, SPF and histological grade. However, introduction of time-dependent co-variates using 2 years as cutoff level showed hypoploidy with a RR of 3.52 and age 540 years with a RR of 3.28 to be independent prognostic 6To whom correspondence and reprint requests should be addressed. Fax: +45 31 38 20 44.
Cytometry, 1992
Tumour DNA ploidy as an independent prognostic factor in breast cancer. Br J Cancer 56:637-642, 1987. Keyhani-Rogfagha S, O'Toole RV, Farrar WB, Sickle-Santanello B, DeCenzo J, Young D: Is DNA ploidy an independent prognostic indicator in infiltrative node-negative breast adenocarcinoma? Cancer 65:1577-1582, 1990. Klintenberg C, Sthl 0, Nordenskjold B, Wallgren A, Arvidsson S, Skoog L: Proliferative index, cytosol estrogen receptor and axil-
Journal of Clinical Pathology, 1999
Aim-To determine the importance of tumour DNA ploidy and cell proliferation, as measured by the S phase fraction (SPF), in relation to other established clinicopathological indicators of prognosis in breast cancer. Methods-A prospective study of 308 patients. Tumours were staged following the TNM system criteria and were classified according to the histological type and grade. DNA flow cytometry was performed on fresh/frozen samples stained with propidium iodide. Hormone receptors were analysed by immunocytochemistry. A Cox proportional hazards regression model was used for statistical evaluation of the prognostic factors. Results-Median follow up time was 39.6 months (range 3 to 84). A DNA diploid pattern was found in 134 tumours (43.5%) and aneuploid in 174 (56.5%). Median SPF value was 6.1% (range 1% to 27.8%). DNA ploidy and SPF were strongly correlated (p < 0.001), and both were related to histological type (p < 0.001), grade of diVerentiation (p < 0.001), tumour size (p = 0.006 and p = 0.002), and hormone receptor activity (p < 0.001). DNA ploidy was also related to node status (p = 0.022), but SPF was not. In univariate analysis, there were significant correlations between disease-free survival and age, histological grade, tumour size, node status, DNA ploidy, SPF, and hormone receptor activity; age, tumour size, node status, DNA ploidy, and hormone receptors were predictors of overall survival. In multivariate analysis, only node status (p = 0.001) and DNA ploidy (p = 0.006) retained independent prognostic significance in relation with overall survival, while node status (p < 0.001) and SPF (p < 0.001) were predictors of disease-free survival. DNA ploidy and SPF continued to predict disease-free and overall survival in lymph node positive (pN1) patients but not in the lymph node negative (pN0) group. Conclusions-DNA ploidy and SPF are strongly intercorrelated and have independent prognostic value for predicting the short term clinical outcome of breast carcinoma patients.
Cytometry, 1995
Flow cytometric (FCM) DNA analysis yields information on ploidy status and the S-phase fraction (SPF), variables of prognostic importance in breast cancer. The clinical value of the SPF is currently being evaluated in prospective randomized trials. The widespread use of FCM DNA analysis emphasizes the importance of reproducibility (both intra-and interlaboratory). In this study, 67 nuclear suspensions of breast cancer samples were analyzed by 12 laboratories routinely performing FCM DNA analysis in breast cancer. No general guidelines were imposed; each laboratory used its own standard protocols. For DNA ploidy status (diploid vs. non-diploid), agreement was complete for 79% (53/67) of the samples, compared with 64% (43/67) of samples when tetraploidy was considered We., euploid (diploid + tetraploid) vs.
One or multiple samplings for flow cytometric DNA analyses in breast cancer-prognostic implications?
Cytometry, 1992
Flow cytometric assessments of DNA ploidy status and the S-phase fraction (SPF) have been shown to yield prognostic information in breast cancer. The aim of the present investigation was to elucidate the reproducibility of results with regard to tumor DNA heterogeneity, and to ascertain whether the prognostic value of DNA measurements might be enhanced by analyzing two pieces of a tumor instead of one.
Relationship between DNA ploidy and survival in patients with primary breast cancer
British Journal of Surgery, 1989
The DNA ploidy of pancreatic cancer tissue from paraffin blocks was measured by flow cytometry in 46 patients whose disease had been detected and treated with surgery. Lymph node involvement was observed at the time of diagnosis in 36% of patients with diploid tumors and in 79% of patients with aneuploid tumors (p = 0.017), but no clear relation to metastasis could be observed (p = 0.201). The S-phase fraction (SPF) was significantly higher in aneuploid than in diploid tumors (p = 0.007). Ail patients who underwent radical surgery had diploid DNA content and SPF below the median (11.5%). Seven patients with a diploid tumor (32%) and none of the aneupioid cases survived 1 year. Over the 1-year period, in order of importance, the type of treatment (p < 0.001), DNA ploidy (p = 0.004), tumor size (p = 0.0046), and lymph node status (p = 0.027) predicted survival. Aneuploidy showed a significant association with decreased cumulative survival 0, = 0.015), and a suggestive relationship with SPF was found. The results suggest that DNA ploidy of pancreatic cancer can be used in dividing the patients into different prognostic groups. The value of the detection of aneuploidy, however, is limited, because diploid pancreatic cancers are also generally rapidly fatal.
Oncology Letters, 2017
The potential prognostic significance of DNA flow cytometric measurements (DNA ploidy and S-phase fraction) in breast cancer remains in dispute. Inconclusive data, primarily due to the lack of consistent standardization and quality control programs, have limited its translation into clinical practice. The aim of the present review, based on the 25-year experience of the Portuguese Institute of Oncology of Lisbon, is to assess the clinical relevance and application of DNA flow cytometry for the prognosis of breast cancer. Overall, data from Portuguese Institute of Oncology of Lisbon indicate that DNA flow cytometry provides significant prognostic information that is biologically relevant and clinically useful for the management of patients with breast cancer. Furthermore, this data has demonstrated the independent value of DNA aneuploidy as a prognostic indicator of poor clinical outcome in various subgroups of patients with early or locally advanced breast cancer at short-and long-term follow-up. Notably, aneuploidy identifies subsets of patients with grade (G)1 or G2 tumours who exhibit a poor clinical outcome. These patients may benefit from adjuvant chemotherapy, particularly those with luminal A and luminal B/human epidermal growth factor-2-negative endocrine-responsive breast cancer. In conclusion, data from Portuguese Institute of Oncology of Lisbon reinforces the clinical importance and utility of DNA flow cytometric analysis, particularly DNA ploidy, in the prognostic assessment and therapeutic planning for patients with breast cancer. Contents
Acta Oncologica, 1992
One frequently used classification of flow cytometric DNA ploidy status (diploid versus nondiploid) was compared with a division into seven ploidy classes based on DNA index (DI) and number of cell populations (hypodiploid, diploid, near-hyperdiploid, hyperdiploid, tetraploid, h ypertetraploid, and multiploid). The latter ploidy classification showed a better correlation with prognosis and other prognostic factors (i.e., lymph node involvement, estrogen and progesterone receptor status, and S-phase fraction). The improvement in correlation was mainly due to the identification of near-hyperdiploid cases (DI 1.00-1.14) which could be combined with the diploid cases to form a group with favourable prognosis. In contrast to cases with a small increase in DNA content (near-hyperdiploid), those with a small decrease of DNA content (hypodiploid) manifested a more aggressive disease. In multivariate analysis, S-phase fraction (SPF) was a more important prognostic factor than both the improved or the conventional ploidy classification.
EVALUATION OF DNA-PLOIDY AND S-PHASE FRACTION ANALYSIS BY FLOW CYTOMETRY IN HUMAN BREAST CARCINOMA
Breast cancer is the most common form of malignancy that affects women. Tumor proliferation can be monitored by measuring DNA synthesis using flowcytometry which provides rapid and precise analysis of large numbers of cells. The aim of the present study was to evaluate DNA ploidy in breast cancer. A number of 85 patients diagnosed with mammary carcinoma and subjected to surgery and different hospital were taken into consideration. None of the patients were subjected to chemo-or radio-therapy prior to surgery. Cell cycle analyses were performed with fresh tumour sample and normal tissue surrounding the tumour. The present study investigate flowcytometric histogram revealed that 25% of the tumour samples showed 62.99% of cells in S phase that were hypodiploid, 25% of subjects with a value of 31.89% were aneuploid and 50% showed a value of 31.89% were aneuploid. Besides, 50% of the samples indicated a S phase value ranging from 9%-20% and were deemed diploid. Data were analysed by the ModFit LT3.1 software provided by Becton Dickinson. Our study indicated that DNA ploidy could be an important factor for estimating the degree of genomic instability which may be reflected by the aggressiveness of the tumor.