DNA content flow cytometry as a prognostic factor for node-positive breast cancer: the role of multiparameter ploidy analysis and specimen sonication
Article Abstract:
Despite improvements in the early diagnosis and treatment of breast cancer, one major question resists resolution: which women with early-stage breast cancer should endure chemotherapeutic treatment when only a few in every hundred actually benefit from this treatment. It would be valuable to successfully predict which women have the best prognosis and therefore do not need adjuvant chemotherapy and which women should receive this therapy to ensure their best chances for survival. One promising method for improving the accuracy of prognosis for breast cancer patients is DNA measurement. In this technique, the DNA content of tumors is measured on a cell-by-cell basis. It may be normal or abnormal, and may indicate that many cells are dividing rapidly or only a few. These measurements may correlate with the patient's prognosis. In most cases, DNA measurement is made by flow cytometry, in which cells are dribbled past lasers one-by-one to obtain optical measurements, which indicate their DNA content. The methods of data analysis most appropriate for breast cancer prognosis are still under investigation; the variability of the technique appears to be great, and different laboratories may obtain different results. The automated flow cytometer does not know if it is looking at a cell nucleus, a clump of cell nuclei, or irrelevant fragments of broken cells; consequently, the resulting data is contaminated by erroneous measurements. In a recent study, researchers attempted to use the scattering of the laser light to reduce the sources of variability in the technique. The way the laser light scatters may be used to distinguish the best measurements from the flawed ones. In examining cells from women with node-positive breast cancer, researchers found that the prognosis was worse when cells had an unusual number of chromosomes (aneuploid), better with a normal number (diploid), and best with exactly twice the normal number of chromosomes (tetraploid). Similarly, patients with indications of greater cell proliferation also had a worse prognosis. However, when the traditional prognostic indicators were included in the statistical analysis, it was found that the prognosis based on both traditional factors and the measurement of DNA was no better than the prognosis based on the traditional factors alone. (Consumer Summary produced by Reliance Medical Information, Inc.)
Publication Name: Cancer
Subject: Health
ISSN: 0008-543X
Year: 1991
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Evaluation of cell proliferation in breast cancer: comparison of Ki-67 immunohistochemical study, DNA flow cytometric analysis, and mitotic count
Article Abstract:
Flow cytometric analysis of DNA has become a popular method of exploring prognostic variables in cancer. Numerous studies have shown that an abnormal amount of DNA, which generally represents aneuploidy, has prognostic value, as do indices of cellular proliferation. Most studies use ethidium bromide as a quantitative fluorescent stain to measure the amount of DNA; there are other possibilities, however. In particular, the antibody Ki-67 may be used to identify replicating cells. When cells are actively traversing the cell cycle, they express an antigen which is recognized by Ki-67. Cells which are busy doing their job and are not replicating do not express this antigen. To evaluate the usefulness of Ki-67 in the prognosis of breast cancer, specimens from 102 breast cancers were examined for Ki-67 staining, microscopic counts of cell division or mitosis, and standard fluorescent DNA measurements. The staining with Ki-67 correlated with high mitotic counts and high tumor grade. Curiously, Ki-67 correlated with the number of cells in the S-phase of the cell cycle in cells which were aneuploid, but not in cells which were diploid. The authors offer no explanation for this, except to say it may be a problem with ''methodology.'' Nevertheless, the staining with Ki-67 seems to correlate well with measures of cell proliferation such as S-phase fraction and mitotic index, as well as measures of tumor aggressiveness such as DNA aneuploidy and tumor grade. Since the antibody is economical and easy to use, it seems likely to be a useful reagent in the evaluation of breast cancer specimens. (Consumer Summary produced by Reliance Medical Information, Inc.)
Publication Name: Cancer
Subject: Health
ISSN: 0008-543X
Year: 1990
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