Familial Cancer

, Volume 15, Issue 2, pp 193–200 | Cite as

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

  • Rosa Murria Estal
  • Sarai Palanca Suela
  • Inmaculada de Juan Jiménez
  • Cristina Alenda Gonzalez
  • Cecilia Egoavil Rojas
  • Zaida García-Casado
  • Jose Antonio López Guerrero
  • María José Juan Fita
  • Ana Beatriz Sánchez Heras
  • Ángel Segura Huerta
  • Ana Santaballa Bertrán
  • Isabel Chirivella González
  • Marta Llop García
  • Gema Pérez Simó
  • Eva Barragán González
  • Pascual Bolufer Gilabert
Original Article

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.

Keywords

BRCAness Copy number aberrations Promoter methylation microRNA expression Immunohistochemical markers 

Notes

Acknowledgments

We would like to thank to the Carlos III Health Institute for having granted the Project PI10/00347. We also would like to thank to the Health Research Institute La Fe for having granted Rosa Murria Estal which made possible her participation in the study. We should thank the effort to perform this work to the pathologists Ana García Martínez (University Hospital La Fe) and Francisco Javier Seguí Ivañez (University Hospital of Alicante), to the laboratory technician Estefania Rojas Calvente (University Hospital of Alicante), to David Hervás statistician of the Health Research Institute La Fe and to Jacobo Martinez Santamaría, Mercedes Goicoechea Sáez and Dolores Salas Trejo (General department of public health, Conselleria de Sanitat, Generalitat Valenciana). Finally we would like to acknowledge the patients enrolled in this study and the Biobank of the General University Hospital of Alicante and the biobank for the biomedical research and public health of the Comunidad Valenciana (IBSP-CV) as part of the Valenciana Biobank Network (RVB) and the National Biobank.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

10689_2015_9864_MOESM1_ESM.pdf (577 kb)
Supplementary material 1 (PDF 576 kb)

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Copyright information

© Springer Science+Business Media Dordrecht 2015

Authors and Affiliations

  • Rosa Murria Estal
    • 1
  • Sarai Palanca Suela
    • 1
  • Inmaculada de Juan Jiménez
    • 1
  • Cristina Alenda Gonzalez
    • 2
  • Cecilia Egoavil Rojas
    • 2
  • Zaida García-Casado
    • 3
  • Jose Antonio López Guerrero
    • 3
  • María José Juan Fita
    • 4
  • Ana Beatriz Sánchez Heras
    • 5
  • Ángel Segura Huerta
    • 6
  • Ana Santaballa Bertrán
    • 7
  • Isabel Chirivella González
    • 8
  • Marta Llop García
    • 1
  • Gema Pérez Simó
    • 1
  • Eva Barragán González
    • 1
  • Pascual Bolufer Gilabert
    • 1
  1. 1.Laboratory of Molecular Biology, Service of Clinical AnalysisUniversity Hospital La FeValenciaSpain
  2. 2.Department of PathologyUniversity General HospitalAlicanteSpain
  3. 3.Laboratory of Molecular BiologyIVOValenciaSpain
  4. 4.Department of OncologyIVOValenciaSpain
  5. 5.Genetic Counseling UnitElche HospitalAlicanteSpain
  6. 6.Genetic Counseling UnitUniversity Hospital La FeValenciaSpain
  7. 7.Department of OncologyUniversity Hospital La FeValenciaSpain
  8. 8.Genetic Counseling UnitClinic University HospitalValenciaSpain

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