Acceleration of chromosomal instability of BRCA1-associated hereditary breast cancers by p53 abnormality.

Chromosomal instability (CIN) of BRCA1-associated hereditary breast cancers was studied by fluorescence in situ hybridization of chromosomes 1, 11, and 17. CIN values (the percentage of cells with a nonmodal chromosome) were obtained for each of three chromosomes, and their average was finally used as the CIN value of the sample. BRCA1-associated tumors showed a significantly (p = 0.0089) higher CIN value than normal breast tissues (24.3 +/- 4.3, n = 7, vs. 9.2 +/- 1.1, n = 6, mean +/- SE). In addition, BRCA1-associated tumors with positive p53 immunostaining showed a significantly (p = 0.0018) higher CIN value than those with negative p53 immunostaining (35.7 +/- 3.5, n = 3, vs. 15.8 +/- 1.3, n = 4). These results demonstrate that a loss of BRCA1 function results in the growth of breast cancers with CIN, and this phenotype is further accelerated by p53 abnormality.