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

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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.

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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.

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Authors and Affiliations

  1. 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

    Rosa Murria Estal, Sarai Palanca Suela, Inmaculada de Juan Jiménez, Marta Llop García, Gema Pérez Simó, Eva Barragán González & Pascual Bolufer Gilabert

  2. Department of Pathology, University General Hospital, Alicante, Spain

    Cristina Alenda Gonzalez & Cecilia Egoavil Rojas

  3. Laboratory of Molecular Biology, IVO, Valencia, Spain

    Zaida García-Casado & Jose Antonio López Guerrero

  4. Department of Oncology, IVO, Valencia, Spain

    María José Juan Fita

  5. Genetic Counseling Unit, Elche Hospital, Alicante, Spain

    Ana Beatriz Sánchez Heras

  6. Genetic Counseling Unit, University Hospital La Fe, Valencia, Spain

    Ángel Segura Huerta

  7. Department of Oncology, University Hospital La Fe, Valencia, Spain

    Ana Santaballa Bertrán

  8. Genetic Counseling Unit, Clinic University Hospital, Valencia, Spain

    Isabel Chirivella González

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  1. Rosa Murria Estal
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Correspondence to Pascual Bolufer Gilabert.

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Murria Estal, R., Palanca Suela, S., de Juan Jiménez, I. et al. Relationship of immunohistochemistry, copy number aberrations and epigenetic disorders with BRCAness pattern in hereditary and sporadic breast cancer. Familial Cancer 15, 193–200 (2016). https://doi.org/10.1007/s10689-015-9864-2

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