Androgen pathway dysregulation in BRCA1-mutated breast tumors
Breast Cancer Research and Treatment , Volume 79 - Issue 1 p. 121- 127
Background. Using array analysis for screening RNA from BRCA1-mutated and sporadic breast tumors, we observed that AIGF/FGF-8 expression was lost in BRCA1-mutated breast tumors. Since this growth factor is induced by androgens, we studied the androgen receptor (AR) expression in BRCA-mutated tumors and in matched sporadic breast tumors. Methods. Paraffin embedded breast tumors of carriers of a BRCA1 mutation (n = 41, median age of patients at time of surgery was 41 years [range 28-59 years]) or a BRCA2 mutation (n = 14, median age 41 years [range 31-85 years]) were analyzed for the presence of ER-alpha, PR, P53 and AR using standard immunohistochemical techniques. All statistical tests used, Pearson χ 2 and Fisher exact, were two-sided. Results. The AR was only present in 12% of BRCA1-mutated tumors, with mutations located at the C-terminal half of the BRCA1-gene. The AR expression was significantly more prevalent, however, in a series of 61 sporadic breast tumors (80%) and in BRCA2-mutated tumors (50%). In contrast to an increased percentage of p53 positive cells, in 66% of the BRCA1-mutated tumors, the ER-alpha expression was observed only in 25% and the PR in 13% of these specimens. The three steroid hormone receptors were expressed in about half of the BRCA2-mutated specimens studied. Conclusions. Our data add to the emerging evidence that the biological phenotype of BRCA1-associated tumors may be different from BRCA2 and non-hereditary cases. The loss of the AR expression, as shown by immunohistochemistry, together with the observed loss of other steroid hormone receptors in BRCA1-mutated tumors may lead to a hormone-independent growth or to anti-hormone resistant growth of these tumors.
|AR, BRCA1, BRCA2, Breast cancer, FGF-8, Immunohistochemistry|
|Breast Cancer Research and Treatment|
|Organisation||Department of Pathology|
Berns, P.M.J.J, Dirkzwager-Kiel, M.J.M, Kuenen-Boumeester, V, Timmermans, A.M, Verhoog, L.C, van den Ouweland, A.M.W, … van der Kwast, Th.H. (2003). Androgen pathway dysregulation in BRCA1-mutated breast tumors. Breast Cancer Research and Treatment, 79(1), 121–127. doi:10.1023/A:1023347409599