The Proliferative Index (PI) of Human Breast Cancer as Obtained by Flow Cytometry

Haag, D.; Goerttler, K; Tschahargane, C

doi:10.1016/s0344-0338(84)80020-5

Cited by 36 publications

(23 citation statements)

References 28 publications

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“…To our knowledcge, there are no published studies in which DNA content determination has been attempted from paraffin embedded material that has been collected in the 1940 s and 1950 s. Although the number of uninterpretable histograms was the greater the older the sample was (data not shown), the majority of the histograms (89%) were of acceptable quality. The histograms were classified without knowledge of survival or clinicopathological data, and the correlations found were stronger than in many series produced from more recent material (Dressler et al, 1988;Feichter et al, 1988;Haag et al, 1984). The percentage of nondiploid tumours found (68%) is almost identical to the mean percentage of 67% found in 23 studies on breast cancer comprising the total of 5,785 patients (data not shown).…”

Section: Discussionmentioning

confidence: 73%

The prognostic significance of nuclear DNA content in invasive breast cancer – a study with long-term follow-up

Toikkanen

Joensuu²,

Klemi³

1989

Br J Cancer

117

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Summary The nuclear DNA content of 351 breast carcinomas was determined by flow cytometry from paraffin-embedded tissue to assess the prognostic significance of DNA ploidy, the DNA index (DI) and the S-phase fraction (SPF). The minimum follow-up of the patients was 22 years, and they were all from a defined urban population. DNA ploidy correlated with histological type and grade, mitotic count and nuclear pleomorphism (P<0.0001), and also with axillary nodal status (P=0.0005), tumour necrosis (P=0.001), primary tumour size (P = 0.03), menopausal status (P = 0.004) and the presence of distant metastases at the time of the diagnosis (P = 0.04). Survival corrected for intercurrent deaths of the patients with a diploid tumour was better than that of the patients with a non-diploid tumour (P = 0.0001, 48% vs 28% at 25 years). SPF Leatham & Brooks, 1987; Slamon et al., 1987).The nuclear DNA content determined by flow cytometry has recently emerged as a new prognostic factor in breast cancer. The technique has gained some popularity, since flow cytometric histograms are rapid to produce and often easy to interpret. It has been suggested that breast carcinomas with an abnormal (non-diploid or aneuploid) nuclear DNA content are associated with less favourable prognosis than carcinomas with a normal (diploid) DNA content (Hedley et al., 1984(Hedley et al., , 1987Coulson et al., 1984;Ewers et al., 1984;Thorud et al., 1986;Baildam et al., 1987;Cornelisse et al., 1987;Kallioniemi et al., 1987;Stal et al., 1989). Similarly, the DNA index (DI, the relative DNA content of an aneuploid stemline of cells as compared with diploid cells) and the percentage of S-phase cells in the DNA histogram (S-phase fraction, SPF) have been found by some to be of prognostic significance (Dowle et al., 1987;Hedley et al., 1987;Kallioniemi et al., 1988;Stal et al., 1989;McDivitt et al., 1986;Klintenberg et al., 1986). However, the prognostic value of nuclear DNA content analysis is still unsettled. Some authors report DNA content to be the most important prognostic variable in breast cancer, and to have independent prognostic value in a multivariate analysis , whereas others find it to have prognostic value only in a univariate analysis (Stal et al., 1989;Hedley et al., 1984), and yet a few fail to find any prognostic significance at all when overall survival is concerned (van der Linden et al., 1989;Uyterlinde et al., 1988;Owainati et al., 1987

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Section: Discussionmentioning

confidence: 73%

The prognostic significance of nuclear DNA content in invasive breast cancer – a study with long-term follow-up

Toikkanen

Joensuu²,

Klemi³

1989

Br J Cancer

117

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“…Obviously the uncorrected S phase portions agree well with published values of other cytometric studies, but they are inconsistent with published results obtained by the 3H-ThdR-LI methods. This discrepancy has already been noticed and discussed (15,16,(24)(25)(26)28,30), but satisfying explanations have been lacking up to now. In the cytometric studies considered (3,5,7,20,29,31,33,34,39), corrections of the debris background levels had been neglected.…”

Section: Discussionmentioning

confidence: 87%

“…Comparison of these data revealed that the cytometrically determined S phase portions were generally higher than those obtained by the alternative method 3H-ThdR-LI (15,16,(24)(25)(26)28,30), but satisfactory reasons for the differences were lacking.…”

mentioning

confidence: 86%

Influence of systematic errors on the evaluation of the S phase portions from DNA distributions of solid tumors as shown for 328 breast carcinomas

et al. 1987

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The portion of cells in S phase has proved to be a valuable prognostic indicator of early relapse and life expectancy, particularly in breast carcinoma. Comparisons of published data on samples of primary breast carcinoma biopsies showed that the values obtained by analyses of flow cytometric DNA distributions were generally higher than those of determinations based on the tritiated thymidine (3H-ThdR) labeling index (LI).Flow cytometric DNA analyses of 328 biopsy samples of primary breast carcinomas revealed that these differences could be explained by varying contributions of debris background. Since this influence is inversely proportional to the cell counts in each channel, it may cause considerable errors, particularly in the S phase channels, which normally contain the lowest counts of the DNA distributions. Two different mathematical rationales were tested in order to separate DNA distributions from the debris superimposition. No appreciable differences were found with respect to the essential results. After appropriate subtraction of the background levels, the previously reported discrepancies between cytometrically determined S phase portions and 3H-ThdR LI values disappeared, and good agreement was achieved for the comparable tumor samples of the present study.In conclusion, debris background subtractions should generally precede the DNA histogram analyses, particularly of solid tumors, in order to obtain reliable S phase values.Key terms: DNA histogram analysis, debris background subtractionThe fraction of cells in DNA synthesis phase is one of the important features derived from flow cytometric DNA distributions. Particularly in breast carcinoma biopsies, the S phase portions proved to be prognostically valuable indicators of the proliferative activity, and correct determinations are therefore required.Numerous data have been published on this subject; such data had been estimated either by the tritiated thymidine (3H-ThdR) labeling index GI) (6,14,17,27,30,32,37,38,40) or by DNA flow cytometry (3,5,7,20,29,31,33,34,39). Comparison of these data revealed that the cytometrically determined S phase portions were generally higher than those obtained by the alternative method 3H-ThdR-LI (15,16,(24)(25)(26)28,30), but satisfactory reasons for the differences were lacking.Although various methods and models for analyses of flow cytometric DNA distributions have been developed and studied exhaustively (survey in 2,10,42,44), little attention has been directed to other influences, such as the debris background level, which may cause errors which are often larger than those resulting from choice of an analytical model. Nevertheless, the few studies of Beck, Haag, and van der Linden (4,15,41) have addressed appropriate subtraction of the debris components on which the actual DNA distributions of intact cell nuclei are superimposed.The rationale of corrections is to define a mathematical function of the debris background distributions which can be subtracted from the originally recorded distribution. Two differ...

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“…Finally, 400 μL PBS was added and the cell cycle distribution was assayed by FACSCalibur flow cytometer (BD Co. Ltd., San Diego, CA, USA) within 45 min. The results were analyzed by ModFit software [8] .…”

Section: Cell Cycle By Flow Cytometry Methodsmentioning

confidence: 99%

Broilerlerde Kitosan Olisakkarit İlavesinin İmmun Organlarda Hücre Siklusu Üzerine Etkileri

Chi¹,

Ding²,

Peng³

et al. 2017

Kafkas Univ Vet Fak Derg

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The objective of this study was to investigate effects of COS on cell cycle and relative weights of thymus, bursa of fabricius (BF) and spleen in broilers. Three hundred and sixty 1-day-old healthy Arbor Acres male broilers were randomly divided into control, COS I, COS II and COS III groups, which were respectively fed with diets containing 0, 200, 350 and 500 mg/kg COS for six weeks. The results showed that the relative weights of immune organs were higher in the COS group II than those in the control group at 42 d. When compared with the control group, increased percentages of G2/M phase thymocytes in the COS groups II and III at 21 d, and decreased percentage of G0/G1 phase cells, increased percentage of G2/M phase cells and PI (proliferation index) of thymus were observed at 42 d. The percentage of G0/G1 phase BF cells was lower, and the percentage of S phase cells and PI of BF were higher in the COS group II at 21 d. The increase of G2/M phase splenocytes and PI, decrease of G0/G1 phase splenocytes in the COS group II could be seen at 42 d. Keywords

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The Proliferative Index (PI) of Human Breast Cancer as Obtained by Flow Cytometry

Cited by 36 publications

References 28 publications

The prognostic significance of nuclear DNA content in invasive breast cancer – a study with long-term follow-up

The prognostic significance of nuclear DNA content in invasive breast cancer – a study with long-term follow-up

Influence of systematic errors on the evaluation of the S phase portions from DNA distributions of solid tumors as shown for 328 breast carcinomas

Broilerlerde Kitosan Olisakkarit İlavesinin İmmun Organlarda Hücre Siklusu Üzerine Etkileri

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