Immunohistochemical, genetic and epigenetic profiles of hereditary and triple negative breast cancers. Relevance in personalized medicine.
This study aims to identify the profile of immunohistochemical (IHC) parameters, copy number aberrations (CNAs) and epigenetic alterations [promoter methylation (PM) and miR expression] related to hereditary (H) and triple negative (TN) breast cancer (BC). This profile could be of relevance for guiding tumor response to treatment with targeting therapy. The study comprises 278 formalin fixed paraffin-embedded BCs divided into two groups: H group, including 88 hereditary BC (HBC) and 190 non hereditary (NHBC), and TN group, containing 79 TNBC and 187 non TNBC (NTNBC). We assessed IHC parameters (Ki67, ER, PR, HER2, CK5/6, CK18 and Cadherin-E), CNA of 20 BC related genes, and PM of 24 tumor suppressor genes employing MLPA/MS-MLPA (MRC Holland, Amsterdam). MiR-4417, miR-423-3p, miR-590-5p and miR-187-3p expression was assessed by quantitative RT-PCR (Applied Biosystems). Binary logistic regression was applied to select the parameters that better differentiate the HBC or TN groups. For HBC we found that, ER expression, ERBB2 CNA and PM in RASSF1 and TIMP3 were associated with NHBC whereas; MYC and AURKA CNA were linked to HBC. For TNBC, we found that CDC6 CNA, GSTP1 and RASSF1 PM and miR-423-3p hyperexpression were characteristic of NTNBC, while MYC aberrations, BRCA1 hypermethylation and miR-590-5p and miR-4417 hyperexpression were more indicative of TNBC. The selected markers allow establishing BC subtypes, which are characterized by showing similar etiopathogenetic mechanisms, some of them being molecular targets for known drugs or possible molecular targets. These results could be the basis to implement a personalized therapy.
Laboratory of Molecular Biology, Service of Clinical Analysis, University Hospital La Fe Valencia, Spain.
Rosa
R
Murria
Laboratory of Molecular Biology, Service of Clinical Analysis, University Hospital La Fe Valencia, Spain.
Sarai
S
Palanca
Laboratory of Molecular Biology, Service of Clinical Analysis, University Hospital La Fe Valencia, Spain.
Inmaculada
I
de Juan
Department of Pathology, University General Hospital Alicante, Spain.
Cristina
C
Alenda
Department of Pathology, University General Hospital Alicante, Spain.
Cecilia
C
Egoavil
Department of Pathology, University General Hospital Alicante, Spain.
Francisco J
FJ
Seguí
Laboratory of Molecular Biology, IVO Valencia, Spain.
Zaida
Z
García-Casado
Department of oncology, IVO Valencia, Spain.
María J
MJ
Juan
Genetic Counseling Unit, Elche Hospital Alicante, Spain.
Ana B
AB
Sánchez
Genetic Counseling Unit, University Hospital La Fe Valencia, Spain.
Ángel
Á
Segura
Department of oncology, University Hospital La Fe Valencia, Spain.
Ana
A
Santaballa
Genetic Counseling Unit, Clinic University Hospital Valencia, Spain.
Isabel
I
Chirivella
Laboratory of Molecular Biology, Service of Clinical Analysis, University Hospital La Fe Valencia, Spain.
Marta
M
Llop
Laboratory of Molecular Biology, Service of Clinical Analysis, University Hospital La Fe Valencia, Spain.
Gema
G
Pérez
Laboratory of Molecular Biology, Service of Clinical Analysis, University Hospital La Fe Valencia, Spain.
Eva
E
Barragán
General Department of Public Health, Conselleria de Sanitat Generalitat Valenciana, Spain.
Dolores
D
Salas
Laboratory of Molecular Biology, Service of Clinical Analysis, University Hospital La Fe Valencia, Spain.
Pascual
P
Bolufer
BRCA1; BRCA2; Sporadic breast cancer; hereditary breast cancer; miR expression profile; molecular markers; mutations