Clonal analysis of bilateral breast cancer.

Forty-nine pairs of bilateral breast tumors (41 synchronous and 8 asynchronous cases) were examined for X-chromosome inactivation status and p53 mutations to address the issue of their clonality. Among 12 cases that were informative for the trinucleotide repeat polymorphism in exon 1 of the androgen receptor gene on the X chromosome, 3 cases were found to have different alleles of the locus inactivated in the right and left breast tumors, indicating that the two tumors arose from distinct transformed cells. Thirteen tumors (13%) from 11 women (22%) contained somatic mutations in exons 5-8 of the p53 gene. In two cases, both breast tumors harbored p53 mutations, but the specific mutations were not identical. Seven synchronous and two asynchronous cases had p53 mutations in one tumor only. A germ line p53 mutation at codon 248, one of the most common p53 mutations in Li-Fraumeni syndrome, was observed in one case. Immunohistochemical analysis of p53 protein with a monoclonal antihuman p53 antibody showed concordant positivity between the right and left tumors in three bilateral breast cancer cases. Our results suggest that at least some bilateral breast tumors originate from distinct cells, but that some bilateral breast tumors may be related through a common p53 abnormality.