Acceleration of chromosomal instability by loss of BRCA1 expression and p53 abnormality in sporadic breast cancers.

ABSTRACT

Correlation of chromosomal instability (CIN) with BRCA1 expression and p53 abnormality was studied in sporadic breast cancers since these genes are implicated in the double strand DNA repair and mitotic checkpoint, and loss of their function is speculated to result in the accumulation of CIN. CIN values (percentage of cells with non-modal chromosomes) were determined by fluorescence in situ hybridization of chromosomes 1, 11, and 17. BRCA1 expression was studied by immunostaining, and p53 abnormality was studied by immunostaining and polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP). CIN values of BRCA1 negative/p53 normal tumors (28.9+/-13.8, n=23) and those of BRCA1 positive/p53 abnormal tumors (27.0+/-2.3, n=3) were not significantly different from those of BRCA1 positive/p53 normal tumors (23.8+/-11.5, n=10). On the other hand, BRCA1 negative/p53 abnormal tumors (41.2+/-12.7, n=23) showed a significant (P<0.01) increase in CIN values than BRCA1 positive/p53 normal tumors. There was no significant association between CIN values and menopausal status, tumor size, histological grade, lymph node status, or estrogen receptor status. These results suggest that BRCA1 down-regulation and p53 abnormality work synergistically to induce CIN in breast cancers, and that clinico-pathological characteristics of breast cancers with high CIN still remain to be established.