Premium
Association between loss of heterozygosity of BRCA1 and BRCA2 and morphological attributes of sporadic breast cancer
Author(s) -
Hanby Andrew M.,
Kelsell David P.,
Potts Henry W.,
Gillett Cheryl E.,
Bishop D. Timothy,
Spurr Nigel K.,
Barnes Diana M.
Publication year - 2000
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/1097-0215(20001015)88:2<204::aid-ijc9>3.0.co;2-1
Subject(s) - loss of heterozygosity , breast cancer , biology , association (psychology) , cancer , pathology , oncology , medicine , genetics , allele , gene , psychology , psychotherapist
Germline mutations in the breast cancer–associated genes BRCA1 and BRCA2 confer a lifetime risk of malignancy. Distinctive morphological features have been attributed to these familial tumours; however, in sporadic breast cancer, the inter‐relationship between loss of heterozygosity (LOH) of these loci and tumour morphology remains to be fully elucidated. We studied a series of 120 sporadic breast carcinomas using microsatellite markers to identify 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 loci 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 at all 4 loci was significantly associated with a high degree of nuclear pleomorphism. Tumours with LOH of BRCA1 also had high mitotic indices, few tubules and a paucity of DCIS, all of which are morphological features similar to those described for familial cases. Following Bonferroni's correction for multiple tests, we found that the tumours with LOH of BRCA1 were still significantly associated with a high mitotic index ( p = 0.0006) and a high degree of nuclear pleomorphism ( p = 0.001). Int. J. Cancer 88:204–208, 2000. © 2000 Wiley‐Liss, Inc.