Chromosome analysis was performed on samples from 85 consecutive patients with breast cancer by one or more of three different methods: direct harvest, culture after mechanical disaggregation, and culture after collagenase digestion. Metaphases suitable for karyotyping were obtained in 70% of the cases; direct harvest yielded metaphases in 29% and cultures without and with digestion in 40% and 59%, respectively. Chromosomal abnormalities were detected in 37 cases. Cells judged to be phenotypically abnormal in culture were twice as likely to reveal chromosomal aberrations as normal-looking cells. Eight cases showed multiclonal abnormalities. Significant differences were detected in the karyotypic profile depending on the method used. With direct harvest, the yield of complex chromosomal changes was 87%, compared to 44% after culture of digested tissue (P < 0.01), and also polyploidy was more common in direct-harvested samples. Detailed karyotypic analysis was possible in 29 primary tumors. The chromosomes most frequently involved were 1, 3, 7, 11, 16, and 17. Recurrent structural abnormalities were der(1;16)(q10;p10), i(1)(q10), del(6)(q21), and del(1)(p22). Breakpoints clustered to the centromere regions of chromosomes 1, 3, 11, 15, and 16 and to the short arms of chromosomes 7, 17, and 19. Seven of twenty-nine fully analyzed cases had a family history of breast cancer, and changes of chromosomes 1, 3, and 15 seemed to be more common in these cases. There was an association between karyotype and survival: The 3 year survival was 63% in patients with complex karyotypic changes and 92% in those without complex changes.
A family is reported which includes five males, two with spina bifida, two sibs with anencephaly, and one with both high and low spinal lesions. The affected subjects came from four sibships in three generations. The mode of inheritance of these neural tube defects is consistent with X linkage.
Breast carcinomas commonly contain varying amounts of fibrous stroma and infiltrates of lymphoid cells. Dickson and Lippman (Endocrine Rev., 8,29, 1987) have proposed a model of growth regulation in breast cancer involving interactions between stroma and carcinoma cells. This model is based on results obtained with established cell lines. In an effort to bring experimentation closer to the clinical situation we have used short-term primary cultures from human breast cancer in co-cultures with lymphocytes and fibroblasts. Cultures were established in a chemically defined serum-free medium (CDM3). Cell types were characterized on the basis of live morphology and expression of vimentin and keratin 18. A semi-quantitative system was developed for measuring growth of epithelial cells, thus defining two indices: maximal growth index (GI-max) and growth rate (GR). Moderate-to-good growth was obtained from 34 out of 46 carcinoma samples (74%) and 30 out of 38 parallel samples of non-cancerous tissue (79%). Success in culture was negatively correlated with the amount of hard stroma but unrelated to age of patient or clinical status. Malignant epithelium was clearly identified in 12 out of 34 (35%) carcinoma samples. For the evaluation of responses of epithelial cells in co-cultures, the cultures from each sample were ranked according to GI-max.(ABSTRACT TRUNCATED AT 250 WORDS)
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