BRCA1 expression in triple negative sporadic breast cancers.
OBJECTIVE
To study how to identify patients with "triple negative" sporadic breast cancers (BCs) having BRCA1 silenced or down-regulated due to epigenetic BRCA1 inactivation.


METHODS
We selected, from our database, patients diagnosed with BC between 1995 and 2001 with tumors exhibiting the "triple negative" phenotype. "Triple positive" tumors were used as controls. BRCA1 protein expression was determined by immunohistochemistry. Methylation specific polymerase chain reaction (PCR) and bisulfite sequencing on genomic DNA were used to assess BRCA1 promoter methylation. BRCA1 m-RNA expression analysis was conducted by real-time PCR.


RESULTS
Forty-four triple negative and 68 controls (triple positive) were eligible for our analysis. BRCA1 promoter methylation was present in 31.8% of triple negative and in 20.6% of triple positive cases. BRCA1 was inactivated (absent BRCA1 m-RNA expression and lack of BRCA1 protein) in 21.4% of tumors with BRCA1 promoter methylation, as compared with 6% of non-methylated ones (p = 0.0453).


CONCLUSIONS
BRCA1 inactivation due to promoter methylation could play an important role in some sporadic BC cases. Patients with this signature could represent the basis for prospective studies aiming to compare clinical response to different drugs.
Galizia
Eva
E
Regional Center of Genetic Oncology, Department of Anatomic and Histologic Pathology and Clinic of Medical Oncology, Ospedali Riuniti, Università Politecnica delle Marche, Ancona, Italy.
Giorgetti
Gessica
G
Piccinini
Gina
G
Santinelli
Alfredo
A
Loretelli
Cristian
C
Bianchi
Francesca
F
Gagliardini
Daniela
D
Carbonari
Giovanna
G
Pisa
Eleonora
E
Belvederesi
Laura
L
Bracci
Raffaella
R
Ferretti
Concetta
C
Corradini
Fabio
F
Cellerino
Riccardo
R
D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000556:secondary; D019175:DNA Methylation; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D009376:Neoplasms, Hormone-Dependent / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D012189:Retrospective Studies; D015996:Survival Rate; D044767:Ubiquitin-Protein Ligases / Q000235:genetics* / Q000378:metabolism
D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D044767:Ubiquitin-Protein Ligases; C111164:BRAP protein, human