Androgen pathway dysregulation in BRCA1-mutated breast tumors.
Breast Cancer Res Treat
; 79(1): 121-7, 2003 May.
Article
en En
| MEDLINE
| ID: mdl-12779088
ABSTRACT
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.
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Colección:
01-internacional
Asunto principal:
Neoplasias de la Mama
/
Receptores Androgénicos
/
Receptores de Esteroides
/
Genes BRCA1
/
Genes BRCA2
/
Mutación
Límite:
Adult
/
Aged
/
Aged80
/
Humans
/
Middle aged
Idioma:
En
Revista:
Breast Cancer Res Treat
Año:
2003
Tipo del documento:
Article
País de afiliación:
Países Bajos