Relationship of immunohistochemistry, copy number aberrations and epigenetic disorders with BRCAness pattern in hereditary and sporadic breast cancer

Fecha de publicación: 01/04/2016

Autores de IIS La Fe

Rosa María Murria Estal

Autor
Sarai Palanca Suela

Autor
Inmaculada De Juan Jiménez

Autor
Ángel Agustín Segura Huerta

Autor
Ana Santaballa Bertrán

Autor
Marta Llop García

Autor
Gema Pérez Simó

Autor
Eva Barragán González

Autor
Pascual Bolufer Gilabert

Autor

Participantes ajenos a IIS La Fe

Gonzalez, CA
Rojas, CE
Garcia-Casado, Z
Guerrero, JAL
Fita, MJJ
Heras, ABS
Gonzalez, IC

Grupos

Hematología y Hemoterapia

Investigador Principal

Javier De La Rubia Comos
Investigación Clínica y Traslacional en Cáncer

Leader

José Gómez Codina

Abstract

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.

Datos de la publicación

ISSN/ISSNe:: 1389-9600, 1573-7292
Tipo:: Article
Páginas:: 193-200
DOI:: 10.1007/s10689-015-9864-2
Factor de Impacto:: 1,015 SCImago ℠
Cuartil:: Q2 SCImago ℠

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Métricas

Filiaciones

Estal, RM:: Univ Hosp La Fe, Serv Clin Anal, Mol Biol Lab, Torre A 4a Planta, Valencia 46026, Spain
Suela, SP:: Univ Hosp La Fe, Serv Clin Anal, Mol Biol Lab, Torre A 4a Planta, Valencia 46026, Spain
Jimenez, ID:: Univ Hosp La Fe, Serv Clin Anal, Mol Biol Lab, Torre A 4a Planta, Valencia 46026, Spain
Gonzalez, CA:: Univ Gen Hosp, Dept Pathol, Alicante, Spain
Rojas, CE:: Univ Gen Hosp, Dept Pathol, Alicante, Spain
Garcia-Casado, Z:: IVO, Mol Biol Lab, Valencia, Spain
Guerrero, JAL:: IVO, Mol Biol Lab, Valencia, Spain
Fita, MJJ:: IVO, Dept Oncol, Valencia, Spain
Heras, ABS:: Elche Hosp, Genet Counseling Unit, Alicante, Spain
Huerta, AS:: Univ Hosp La Fe, Genet Counseling Unit, Valencia, Spain
Bertran, AS:: Univ Hosp La Fe, Dept Oncol, Valencia, Spain
Gonzalez, IC:: Clin Univ Hosp, Genet Counseling Unit, Valencia, Spain
Garcia, ML:: Univ Hosp La Fe, Serv Clin Anal, Mol Biol Lab, Torre A 4a Planta, Valencia 46026, Spain
Simo, GP:: Univ Hosp La Fe, Serv Clin Anal, Mol Biol Lab, Torre A 4a Planta, Valencia 46026, Spain
Gonzalez, EB:: Univ Hosp La Fe, Serv Clin Anal, Mol Biol Lab, Torre A 4a Planta, Valencia 46026, Spain
Gilabert, PB:: Univ Hosp La Fe, Serv Clin Anal, Mol Biol Lab, Torre A 4a Planta, Valencia 46026, Spain