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

Correlation of chromosomal instability (CIN) with BRCA1 expression and p53 abnormality was studied in sporadic breast cancers since these genes are im plicated in the double strand DNA repair and mitotic checkpoint, and loss o f their function is speculated to result in the accumulation of GIN. CIN va lues (percentage of cells with non-modal chromosomes) were determined by fl uorescence in situ hybridization of chromosomes 1, 11, and 17. BRCA1 expres sion was studied by immunostaining, and p53 abnormality was studied by immu nostaining and polymerase chain reaction-single-strand conformation polymor phism (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/p5 3 abnormal tumors (41.2 +/- 12.7, n = 23) showed a significant (P < 0.01) i ncrease in CIN values than BRCA1 positive/p53 normal tumors. There was no s ignificant 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 synerg istically to induce CIN in breast cancers, and that clinico-pathological ch aracteristics of breast cancers with high CIN still remain to be establishe d. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.