A practical graphical method for estimating the fraction of cells in S in DNA histograms from clinical tumor samples containing aneuploid cell populations

Ritch, Paul S.; Shackney, Stanley E.; Schuette, William H.; Talbot, Thomas; Smith, Charles A.

doi:10.1002/cyto.990040110

Cited by 39 publications

(14 citation statements)

References 10 publications

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“…S fractions were calculated from the DNA histograms by the method of Ritch et al (21), and aneuploidy peaks were identified and characterized using previously described criteria (24). Specifically, the identification of nontetraploid aneuploidy required the presence of a peak that was at least partially separated from the G, or G,M peak, and contained at least 5% of the cells in the population.…”

Section: Dna Histogram Analysesmentioning

confidence: 99%

Origins and clinical implications of aneuploidy in early bladder cancer

et al. 1995

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Cytogenetic and flow cytometric studies in a variety of human solid tumors have suggested that gross aneuploidy may arise by a process of abrupt chromosome complement doubling followed by gradual chromosome loss. However, this sequence has not been demonstrated directly in serial studies in individual patients in vivo. The purpose of this study was to search for evidence of chromosome complement doubling and subsequent chromosome loss in flow cytometric ploidy patterns in serial bladder washings and/or biopsies from individual patients with early bladder cancer. Fifty-two patients with noninvasive bladder cancer were followed with serial flow cytometric DNA studies for periods ranging from 5.1 to 42.7 months (median 15.1 months). Serial changes in DNA ploidy and S phase fractions were recorded and correlated with histologic and/or cytologic findings, response to treatment and clinical outcome. The data suggest a series of genetic evolutionary changes in early bladder cancer that include the initial development of peridiploid aneuploidy and repeated rounds of DNA content doubling with chromosome loss in patients with progressive disease. It is likely that gross DNA aneuploidy, and more specifically, DNA multiploidy and DNA hypertetraploidy, all arise by this mechanism. The sequence of DNA diploidy, peridiploid aneuploidy, neartetraploidy, hypotetraploidy and hypertetraploidy is associated with a progressive increase in S phase fraction, and with increasing tumor grade; late steps in this ploidy sequence were often present in tumors that were refractory to local therapeutic measures and tumors that developed deep tumor invasion and/or distant metastases. We conclude that DNA multiploidy and hypertetraploidy are markers of advanced stages of genetic evolution in human bladder cancer. o 1995 Wiley-Liss, Inc.Key terms: Aneuploidy, bladder cancer, prognosis, flow cytometry, tetraploidization Unlike the leukemias, human solid tumors frequently exhibit gross aneuploidy, with chromosome counts often in the range of 60-90 per cell (or a DNA index of 1.3 or greater by flow cytometric DNA analysis). While gross aneuploidy has been implicated in the development and progression of many human solid tumors, its value as a clinical prognostic factor has been controversial. In a recent consensus conference sponsored by the National Cancer Institute, a panel of experts concluded that aneuploidy is a useful prognostic factor in such tumors as ical methods might be helpful in uncovering statistical interactions among various clinical prognostic factors. However, a more fundamental understanding of the biology of the various genetic processes that drive tumor evolution and the mechanisms that underlie the interactions among them may ultimately provide more useful clinical prognostic information.Received for publication June 21, 1994; accepted May 1, 1995. This work was supported by Allegheny-Singer Research Institute grant superficial bladder cancer (34) and in prostate cancer (26), but is not an independent prognostic factor in br...

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Section: Dna Histogram Analysesmentioning

confidence: 99%

Origins and clinical implications of aneuploidy in early bladder cancer

et al. 1995

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“…From these graphs, individual debris contamination was determined as constants of a "background function" subtracted from the original frequency distribution in order to obtain a "cleaned" distribution ( were determined independently by the computerized Dean and Jett model (2) as well as graphically from the cumulative frequency curves (integral curves) of the "cleaned" DNA distributions, based on the trapezoidal model (19). Cell clumping artifacts such as doublets and triplets were eliminated mathematically using a modification of the formula given by Beck (1).…”

Section: Dna Flow Cytometry (Fcm)mentioning

confidence: 99%

“…For control of the validity of the graphical SPF values, two independent methods were used the Dean and Jett model (2) and a graphic method (19).…”

Section: Introductionmentioning

confidence: 99%

Comparison of S‐phase fractions measured by flow cytometry and autoradiography in human transplant tumors

et al. 1988

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The "H-thymidine labeling index (TLI) and the percentage of cells in the S-phase have been determined by autoradiography and by flow cytometry, (FCM), respectively, in six malignant tumors of human origin transplanted on athymic nude mice. The Dean and Jett model and the graphical model were used to determine the percent of S-phase cells by FCM. Cell cycle analysis was performed using 1) no correction for background; 2) an algebraic function for background correction; and 3) an exponential function for background subtraction. Each of these three data sets was evaluated using both the Dean and Jett model and a graphical model for the evaluation of DNA histograms. The S-phase fractions (SPF) were compared to the corresponding labeling index results.SPF without background correction were 1.54 times higher than the TLI. SPF, after correction using the algebraic model, were 1.29-fold higher than the TLI, whereas SPF obtained after background subtraction according to the exponential model were only 1.05-fold higher than the TLI. Student's t-test revealed significant differences between the mean TLI values (16.

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“…Determination of the fraction of cells in S phase. The fraction of cells in S was determined by the method of Ritch et al (53). In diploidaneuploid mixtures that could be resolved either graphically or by dual parameter analysis, S fractions were calculated separately for each subpopulation.…”

Section: Clinical Samplesmentioning

confidence: 99%

The biology of tumor growth in the non-Hodgkin's lymphomas. A dual parameter flow cytometry study of 220 cases.

Shackney¹,

Levine²,

Fisher³

et al. 1984

J. Clin. Invest.

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Abstract. Dual parameter flow cytometry studies (cell DNA content and electronic cell volume) were performed in 220 cases of non-Hodgkin's lymphoma. All cases were characterized as B or T cell malignancies, based on immunologic surface marker characteristics. Aneuploidy by flow cytometry was more common among the B cell lymphomas than among the T cell lymphomas, and was most common among the large B ponents could often be separated from other components of the mixture in multiparameter studies on the basis of the larger electronic cell volumes of the aneuploid cells. In each case, the aneuploid large cell component almost invariably had a higher S fraction than the residual component(s) of the mixture. Overall, the data are consistent with a model of clonal selection and clonal evolution in the lymphomas in which early cytogenetic abnormalities that involve little or no change in total cell DNA content are followed by cell tetraploidization that is associated with cytogenetic instability and chromosome loss over the course of time.

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A practical graphical method for estimating the fraction of cells in S in DNA histograms from clinical tumor samples containing aneuploid cell populations

Cited by 39 publications

References 10 publications

Origins and clinical implications of aneuploidy in early bladder cancer

Origins and clinical implications of aneuploidy in early bladder cancer

Comparison of S‐phase fractions measured by flow cytometry and autoradiography in human transplant tumors

The biology of tumor growth in the non-Hodgkin's lymphomas. A dual parameter flow cytometry study of 220 cases.

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