Association of loss of BRCA1 expression with centrosome aberration in human breast cancer.

Centrosome aberration in number and/or size is reportedly often observed in human breast cancer. The aim of this study was to investigate the relationship between centrosome aberration and chromosomal instability as well as the expression of centrosome regulators such as BRCA1, Aurora-A, and p53.,Centrosome aberration in number and size was determined immunohistochemically using the anti-gamma-tubulin antibody, and chromosomal instability was evaluated by fluorescence in situ hybridization analysis of chromosomes 1, 11, and 17 in paraffin sections from 50 human breast cancers. Immunohistochemical examination of BRCA1, Aurora-A, and p53 was also performed to examine the relationship of their expression with centrosome aberration.,Percentage of tumor cells with centrosome aberration in size varied from 0.9 to 30.4% (median 9.5%) and in number it varied from 0.5 to 86.5% (median 34.5%) in each tumor. No significant association in number or size, however, was observed between chromosomal instability and centrosome aberration. Numerical centrosome aberration was significantly associated with negative BRCA1 expression (P = 0.001). Breast tumors (n = 3) from patients with a proven BRCA1 germline mutation also showed a significant relationship with numerical centrosome aberration (P = 0.011). On the other hand, expression of Aurora-A or p53 was not significantly associated with centrosome aberration in either number or size.,Centrosome aberration is not associated with chromosomal instability, indicating the importance of other mechanisms in the induction of chromosomal instability in human breast cancer. BRCA1, but not Aurora-A and p53, is significantly involved in the pathogenesis of centrosome aberration.