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  • 1
    Electronic Resource
    Electronic Resource
    The functional relationship between in vivo bromodeoxyuridine labeling index and Ki-67 proliferation index in human breast cancer (1998)
    Springer
    Breast cancer research and treatment 49 (1998), S. 155-164 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; bromodeoxyuridine ; functional relationship ; human study ; in vivo ; Ki-67 ; prognosis ; proliferation markers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Proliferation indices are used, along with other parameters, to estimate the risk of recurrence of breast cancer for individual patients. Because it is unlikely one index will be practical for all patients, it is important to understand the relationship between various indices of proliferation. For this reason, we compared a proliferation index based on in vivo labeling of S-phase tumor cells with the thymidine analog bromodeoxyuridine (BrdUrd), to a proliferation index based on an estimate of the growth fraction with the MIB-1 antibody to the Ki-67 antigen. With informed consent, we gave 145 patients 200 mg/m2 BrdUrd intravenously just prior to surgical removal of breast cancer. On histology sections, we visually counted S-phase cells which had incorporated BrdUrd using the Br-3 antibody which is specific to DNA-incorporated BrdUrd, and we counted cells in the growth fraction using the MIB-1 antibody to the Ki-67 antigen. We found that both indices were positively correlated with tumor size, number of positive nodes, and tumor grade, and both were negatively correlated with age and estrogen-progesterone receptor positivity. Using a linear functional relationship model, we found that the best (i.e. the maximal) fit between the two indices (correlation coefficient 0.79; p 〈 0.0001) occurred when each index was square root transformed, as is appropriate when counts follow a Poisson distribution. When we used the median as a cutpoint for each index, the classification of 19 percent of data pairs changed depending upon which index was used. We also estimated that the Ki-67 intercept (1.02 ± 0.25) was significantly greater than zero. We conclude that the BrdUrd index of DNA synthesis in S-phase correlates highly with the MIB-1 index of the growth fraction, and both indices correlate well with other parameters of tumor aggressiveness. Because this correlation is driven by concordance of the extremes of high and low counts, clinical comparison will be necessary to determine which is the better prognostic marker for human breast cancer.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1005926228093
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    Paper (German National Licenses)
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  • 2
    Electronic Resource
    Electronic Resource
    The prognostic value of proliferation indices: a study with in vivo bromodeoxyuridine and Ki-67 (2000)
    Springer
    Breast cancer research and treatment 59 (2000), S. 113-123 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; bromodeoxyuridine ; Ki-67 ; nodes ; survival ; S-phase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Proliferation indices are intended to help patients and clinicians make treatment decisions. We have previously demonstrated that a proliferation index based on in vivo labeling of S-phase cells with bromodeoxyuridine (BrdUrd) correlates with Ki-67 labeling index (LI). We now compare the prognostic value of these indices. With written consent, we gave 129 women with biopsy confirmed breast cancer 200 mg/M2 BrdUrd during 30 min immediately preceding surgery. We used IU-4 anti BrdUrd antibody to count the immunohistochemical labeling index (LI) of DNA-incorporated BrdUrd in 2,000 cells and MIB-1 to count Ki-67 (118 cases). Patients received standard surgical and adjuvant treatment. No patients were lost to follow-up and patients were followed a minimum of 2 (median 5.1) years. We compared survival and recurrence in tumors with high vs low labeling indices. We found that women in the low BrdUrd LI group had better disease free survival (92% vs 67% 5-yr DFS p = 0.001) and overall survival (94% vs 70% 5-yr OS, p = 0.0001) than those with a high LI. In comparison, a low Ki-67 index predicted better OS (87% vs 80% 5-yr OS, p = 0.020) and a trend for better DFS (84% vs 72% DFS p = 0.055). The apparent superiority of BrdUrd LI over Ki-67 LI is likely due to chance (p = 0.18). In multivariate survival analyses we found that BrdUrd LI proliferative index significantly improves prediction of DFS or OS even when node status, age or tumor size is in the model. We conclude that markers of proliferation are useful adjuncts in predicting patient prognosis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006344010050
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    Paper (German National Licenses)
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  • 3
    Electronic Resource
    Electronic Resource
    Cell dissociation techniques in human breast cancer — Variations in tumor cell viability and DNA ploidy (1989)
    Springer
    Breast cancer research and treatment 13 (1989), S. 153-159 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; DNA ploidy ; viability ; enzymatic dissociation ; mechanical dissociation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Approximately 70% of breast cancers contain cell populations with hyperdiploid (〉G0/G1) DNA content; however, cells cultured from breast cancers have only diploid DNA contents and karyotypes. Mechanically dissociated cells rarely, if ever, grow in culture, while enzymatically dissociated cells do grow in most cases. To determine if cell dissociation techniques used to prepare cells for culture and other laboratory procedures select for cells with specific features, and if tumor cells are killed in the process, breast cancer cells obtained by mechanical dissociation and by enzymatic dissociation were examined for DNA content and cell viability (measured by dye exclusion). Mechanical dissociation yielded more dead cells and cells with hyperdiploid (〉G0/G1) DNA than did enzymatic dissociation. Hyperdiploid cells were also found in the dye-excluding population with each dissociation technique, suggesting that the hyperdiploid cells were not always dead. We conclude that,in vivo, tumors contain cellular subpopulations with low viability and hyperdiploid (〉G0/G1) DNA patterns. The extent to which these subpopulations are present in a sample depends on the dissociation technique employed. That only diploid cells are found in cultures of primary breast cancers may be because enzymatic dissociation, used to prepare cells for culture, yields predominantly diploid cells. These observations also have important implications for interpreting measurements made on dispersed cells,e.g., viability, DNA content, and other cytochemical markers.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01806527
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    Paper (German National Licenses)
    Fulltext
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