Association between loss of heterozygosity of BRCA1 and BRCA2 and morphological attributes of sporadic breast cancer

Germline mutations in the breast cancer-associated genes BRCA1 and BRCA2 co nfer a lifetime risk of malignancy. Distinctive morphological features have been attributed to these familiar tumours; however, in sporadic breast can cer, the inter-relationship between loss of heterozygosity (LOH) of these l oci and tumour morphology remains to be fully elucidated. We studied a seri es of 120 sporadic breast carcinomas using microsatellite markers to identi fy LOH of BRCA1, BRCA2, p53 and PTEN, The associations between loss at each of the loci were examined and related to tumour morphology. LOH of the 4 l oci did not occur independently; there were highly significant associations between LOH of BRCA1 and both BRCA2 (p < 0.001) and p53 (p < 0.001). LOH a t all 4 loci was significantly associated with a high degree of nuclear ple omorphism, Tumours with LOH of BRCA1 also had high mitotic indices, few tub ules and a paucity of DCIS, all of which are morphological features similar to those described for familial cases. Following Bonferroni's correction f or multiple tests, we found that the tumours with LOH of BRCA1 were still s ignificantly associated with a high mitotic index (p = 0.0006) and a high d egree of nuclear pleomorphism (p = 0.001). Int. J. Cancer 88:204-208, 2000, (C) 2000 Wiley-Liss, Inc.