Androgen pathway dysregulation in BRCA1-mutated breast tumors.

Autor: Berns EM; Department of Medical Oncology, Josephine Nefkens Institute, Erasmus MC, Rotterdam, The Netherlands. p.m.j.j.berns@erasmusmc.nl, Dirkzwager-Kiel MJ, Kuenen-Boumeester V, Timmermans M, Verhoog LC, van den Ouweland AM, Meijer-Heijboer H, Klijn JG, van der Kwast TH
Jazyk: angličtina
Zdroj: Breast cancer research and treatment [Breast Cancer Res Treat] 2003 May; Vol. 79 (1), pp. 121-7.
DOI: 10.1023/a:1023347409599
Abstrakt: 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 chi2 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.
Databáze: MEDLINE
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