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  • 1
    ISSN: 0921-8734
    Keywords: Ageing ; Aneuploidy ; Chromosome ; Lymphocytes ; human
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1573-7217
    Keywords: breast cancer ; cytogenetics ; estrogen receptor ; genetic evolution ; ploidy ; progesterone receptor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The expression of estrogen (ER) and progesterone (PR) receptors was assayed by steroid binding in a series of 95 malignant breast tumors, for which the analysis of chromosome aberrations was performed and allowed the reconstruction of their chromosomal evolution. It was shown that breast tumors undergo a progressive loss of chromosomes, with occasionally one and rarely two endoreduplications. Chromosome losses were often the consequence of rearrangements, and the rate of rearranged chromosomes, which increases progressively, appeared as a possible indicator of tumor progression. The distribution of ER and PR values in the sample of 95 tumors was compared to that of a larger control series of consecutive cases: 598 for ER and 460 for PR. The similarities of the distributions indicated that the sample of 95 tumors was representative of the general population of breast cancers. The levels of ER and PR expression were very strongly and negatively correlated to the rate of rearranged chromosomes, but not to the modal number of chromosomes. However, when tumors having either undergone endoreduplication or not (〉50 or 〈51 chromosomes, respectively) were considered separately, a significant correlation between ER and PR expression and chromosome number was found within each group. Finally, breast cancers were subdivided into 4 stages of cytogenetic evolution, from the least to the most evolved: stage 1: ≤50 chromosomes, 〈25% rearranged chromosomes; stage 2: 〉50 chromosomes, 〈25% rearranged chromosomes; stage 3: ≤50 chromosomes, 〉25% rearranged chromosomes; stage 4: 〉50 chromsomes, 〉25% rearranged chromosomes. The rate of negative or low ER values (〈500 fmol/g tissue) was 10% in stage 1; 16% in stage 2; 45% in stage 3; 82% in stage 4. The corresponding rates for negative or low PR values (〈500 fmol/g tissue) were 17%; 28%; 60%; and 91%. These data illuminate the probable role of genetic evolution in determining the variations of biological prognostic parameters of breast cancer, such as steroid hormone receptors.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1573-7217
    Keywords: breast cancer evolution ; chromosome rearrangements ; cytogenetics ; DNA ploidy ; progression ; proliferative activity ; S-phase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The prognostic value of proliferative activity and its relationship with steroid hormone receptors and histopathological grade have been demonstrated for breast cancers. However, nothing is known about the underlying mechanisms. In order to understand the chronology of the appearance of increased proliferative activities, we used a series of 760 consecutive breast cancers for which we had obtained S-phase fractions (SPFs) by DNA flow cytometry. When the absolute difference from a DNA index of 1.00 was compared to SPFs, a significant positive correlation was obtained (r=0.39, p〈0.0001), indicating that the probability of observing a high SPF increases when tumors progressively deviate from diploidy. A highly significant correlation was observed for the hyperploid group when hypertetraploid tumors were excluded, as the SPFs increased progressively as the DNA indices decreased from 2.00 to 1.30. This observation suggested a relationship with the evolution of chromosomal abnormalities as determined by cytogenetic analysis. Indeed, in a subset of 52 cases for which sufficient metaphases were available, there was a highly significant correlation between the SPF values and the proportion of rearranged chromosomes in the tumor cells (r=0.60, p〈0.0001). When SPFs were separated into low or high using the median value (4.5%), a correlation also existed with the genetic evolution, since they increased from diploidy to hypodiploidy and then, after endoreduplication, from tetraploidy towards triploidy, as determined by the chromosome counts. Our results substantiate the relationship between proliferative activity and steroid hormone receptors which follow the same model. Therefore, it seems probable that the high proliferative activity of breast cancers indicates a state of genetic evolution which in turn may explain the prognostic significance.
    Type of Medium: Electronic Resource
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