THE ROLE OF P53 MUTATIONS IN BILATERAL BREAST-CARCINOMA

Mutations of the tumor suppressor gene p53 have been implicated in cer tain familial cases of breast cancer. We examined a series of 38 cases of nonfamilial bilateral breast cancer using antibodies CM1 and DO7 t o p53 wild-type and mutant protein (Novocastra Laboratories) by the av idin-biotin-peroxidase complex method. The two antibodies reacted simi larly. Mutant p53 protein was detected in 17 of 76 (22%) tumors but in only 3 of 38 (8%) paired tumors. There were no significant difference s in p53 expression between synchronous (<12 mos) and metachronous tum ors (29% vs 17%, P = 0.09) or between first and second tumors (14% vs 26%, P = 0.29). Mutant p53 was detected bilaterally in one metachronou s and two synchronous cases, which were amplified and sequenced by pol ymerase chain reaction and single strand confirmation polymorphism. On e synchronous case showed a bilateral mutation in exon 2-3; the other had a bilateral mutation in exon 8-9. In the metachronous case, a muta tion could be demonstrated in only one breast. Analysis of all tumors demonstrated that when p53 protein is overexpressed in the first tumor , there is a 60% probability of overexpression in the second, whereas if absent from the first, it is unlikely to be present in the second. These data suggest that p53 mutations do not play a major role in the pathogenesis of bilateral disease in most women.