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[173] Using Morphology and Phenotype To Predict BRCA1 Mutation Carrier Status in Breast Cancer
AM Mulligan, N Weerasooriya, IL Andrulis, FP O'Malley. Mount Sinai Hospital, Toronto, ON, Canada; Toronto, ON, Canada
Background: The basal phenotype has been shown to be disproportionately represented in breast cancers from BRCA1 mutation carriers. Our aim in this large series of patients with BRCA1 associated breast cancers, was to use an extended panel of biomarkers to further characterize tumors in BRCA1 mutation carriers.
Design: Tissue microarrays (TMAs) were constructed from tumors from 59 BRCA1 carriers and 57 control patients selected from the Ontario Familial Breast Cancer Registry. Immunohistochemical analysis of ER, PgR, HER2, p53, CK5, CK8/18, MIB-1, CK14, p27, cyclin D1 and vimentin was performed on the TMAs from carriers and controls and scored using Allreds method.
Results: Tumors from BRCA1 mutation carriers were higher grade (Odds ratio (OR) 42.7), showed a marked lymphocytic infiltrate (OR 5.50) and a syncytial growth pattern (OR 5.50). BRCA1-associated tumors were ER/PgR/HER2 negative and CK5 positive, in keeping with a basal phenotype. In addition, these tumors were more frequently p53 positive, had a high MIB-1 index and were negative for CK8/18, cyclin D1 and p27 (Table 1).
Conclusions: We have confirmed, in a large series of patients with known BRCA1 mutations, that these tumors cluster with the basal phenotype. Additionally, we have demonstrated that they have a high MIB-1 index, are p53 postive, but lack p27, cyclin D1 and CK8/18 expression. The combination of these specific morphologic and phenotypic features could be used to more specifically target genetic testing in the appropriate clinical setting.
Table 1| Biomarker | BRCA1 mutation carriers N(%) | Non-carriers N(%) | Odds Ratio | Chi-square (p-value) |
|---|
| ER | 9(15) | 29(51) | 0.16 | 17.5 (0.0002) |
|---|
| PR | 4(7) | 19(33) | 0.13 | 15.7 (0.0004) |
|---|
| p53 | 31(53) | 10(18) | 5.68 | 15.5 (0.0004) |
|---|
| CK8/18 | 12(20) | 30(53) | 0.18 | 13.7 (0.001) |
|---|
| CK5 | 34(58) | 4(7) | 17.35 | 24.9 (<0.0001) |
|---|
| Cyclin D1 | 2(3) | 6(11) | 0.23 | 5.3 (0.07) |
|---|
| MIB-1 | 13(22) | 1(2) | 18.38 | 8.0 (0.02) |
|---|
| CK14 | 9(15) | 3(5) | 3.46 | 4.7 (0.09) |
|---|
| p27 | 1(2) | 14(25) | 0.06 | 8.3 (0.02) |
|---|
| Vimentin | 4(7) | 0(0) | 5.64 | 1.7 (0.43) |
|---|
| HER2 | 1(2) | 2(4) | 0.45 | 0.4 (0.81) |
|---|
Odds ratio of biomarker expression in BRCA1 mutation carriers vs.controls. N(%)=number and percentage of patients with positive expression of biomarker
Category: Breast
Monday, March 26, 2007 8:15 AM
Platform Session: Section D, Monday Morning
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