Relationship of immunohistochemistry, copy number aberrations and epigenetic disorders with BRCAness pattern in hereditary and sporadic breast cancer.
Por:
Murria Estal R, Palanca Suela S, de Juan Jiménez I, Alenda C, Egoavil C, García-Casado Z, López Guerrero JA, Juan Fita MJ, Sánchez Heras AB, Segura Huerta Á, Santaballa Bertrán A, Chirivella González I, Llop García M, Pérez Simó G, Barragán González E and Bolufer Gilabert P
Publicada:
1 abr 2016
Resumen:
The study aims to identify the relevance of immunohistochemistry (IHC), copy number aberrations (CNA) and epigenetic disorders in BRCAness breast cancers (BCs). We studied 95 paraffin included BCs, of which 41 carried BRCA1/BRCA2 germline mutations and 54 were non hereditary (BRCAX/Sporadic). Samples were assessed for BRCA1ness and CNAs by Multiplex Ligation-dependent Probe Amplification (MLPA); promoter methylation (PM) was assessed by methylation-specific-MLPA and the expression of miR-4417, miR-423-3p, miR-590-5p and miR-187-3p by quantitative RT-PCR. IHC markers Ki67, ER, PR, HER2, CK5/6, EGFR and CK18 were detected with specific primary antibodies (DAKO, Denmark). BRCAness association with covariates was performed using multivariate binary logistic regression (stepwise backwards Wald option). BRCA1/2 mutational status (p = 0.027), large tumor size (p = 0.041) and advanced histological grade (p = 0.017) among clinic-pathological variables; ER (p < 0.001) among IHC markers; MYC (p < 0.001) among CNA; APC (p = 0.065), ATM (p = 0.014) and RASSF1 (p = 0.044) among PM; and miR-590-5p (p = 0.001), miR-4417 (p = 0.019) and miR-423 (p = 0.013) among microRNA expression, were the selected parameters significantly related with the BRCAness status. The logistic regression performed with all these parameters selected ER+ as linked with the lack of BRCAness (p = 0.001) and MYC CNA, APC PM and miR-590-5p expression with BRCAness (p = 0.014, 0.045 and 0.007, respectively). In conclusion, the parameters ER expression, APC PM, MYC CNA and miR-590-5p expression, allowed detection of most BRCAness BCs. The identification of BRCAness can help establish a personalized medicine addressed to predict the response to specific treatments.
Filiaciones:
Murria Estal R:
Laboratory of Molecular Biology, Service of Clinical Analysis, University Hospital La Fe, Torre A 4ª planta, Avenida de Fernando Abril Martorell, no 106, 46026, Valencia, Spain
Palanca Suela S:
Laboratory of Molecular Biology, Service of Clinical Analysis, University Hospital La Fe, Torre A 4ª planta, Avenida de Fernando Abril Martorell, no 106, 46026, Valencia, Spain
de Juan Jiménez I:
Laboratory of Molecular Biology, Service of Clinical Analysis, University Hospital La Fe, Torre A 4ª planta, Avenida de Fernando Abril Martorell, no 106, 46026, Valencia, Spain
Alenda C:
Department of Pathology, University General Hospital, Alicante, Spain
Egoavil C:
Department of Pathology, University General Hospital, Alicante, Spain
García-Casado Z:
Laboratory of Molecular Biology, IVO, Valencia, Spain
López Guerrero JA:
Laboratory of Molecular Biology, IVO, Valencia, Spain
Juan Fita MJ:
Department of Oncology, IVO, Valencia, Spain
:
Genetic Counseling Unit, Elche Hospital, Alicante, Spain
Segura Huerta Á:
Genetic Counseling Unit, University Hospital La Fe, Valencia, Spain
Santaballa Bertrán A:
Department of Oncology, University Hospital La Fe, Valencia, Spain
Chirivella González I:
Genetic Counseling Unit, Clinic University Hospital, Valencia, Spain
Llop García M:
Laboratory of Molecular Biology, Service of Clinical Analysis, University Hospital La Fe, Torre A 4ª planta, Avenida de Fernando Abril Martorell, no 106, 46026, Valencia, Spain
Pérez Simó G:
Laboratory of Molecular Biology, Service of Clinical Analysis, University Hospital La Fe, Torre A 4ª planta, Avenida de Fernando Abril Martorell, no 106, 46026, Valencia, Spain
Barragán González E:
Laboratory of Molecular Biology, Service of Clinical Analysis, University Hospital La Fe, Torre A 4ª planta, Avenida de Fernando Abril Martorell, no 106, 46026, Valencia, Spain
Bolufer Gilabert P:
Laboratory of Molecular Biology, Service of Clinical Analysis, University Hospital La Fe, Torre A 4ª planta, Avenida de Fernando Abril Martorell, no 106, 46026, Valencia, Spain.
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