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Phenotypic characterization of BRCA1 and BRCA2 tumors based in a tissue microarray study with 37 immunohistochemical markers

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Summary

Familial breast cancers that are associated with BRCA1 or BRCA2 germline mutations differ in both their morphological and immunohistochemical characteristics.

To further characterize the molecular difference between genotypes, the authors evaluated the expression of 37 immunohistochemical markers in a tissue microarray (TMA) containing cores from 20 BRCA1, 14 BRCA2, and 59 sporadic age-matched breast carcinomas. Markers analyzed included, amog others, common markers in breast cancer, such as hormone receptors, p53 and HER2, along with 15 molecules involved in cell cycle regulation, such as cyclins, cyclin dependent kinases (CDK) and CDK inhibitors (CDKI), apoptosis markers, such as BCL2 and active caspase 3, and two basal/myoepithelial markers (CK 5/6 and P-cadherin). In addition, we analyzed the amplification of CCND1, CCNE, HER2 and MYC by FISH.

Unsupervised cluster data analysis of both hereditary and sporadic cases using the complete set of immunohistochemical markers demonstrated that most BRCA1-associated carcinomas grouped in a branch of ER-, HER2-negative tumors that expressed basal cell markers and/or p53 and had higher expression of activated caspase 3. The cell cycle proteins associated with these tumors were E2F6, cyclins A, B1 and E, SKP2 and Topo IIα. In contrast, most BRCA2-associated carcinomas grouped in a branch composed by ER/PR/BCL2-positive tumors with a higher expression of the cell cycle proteins cyclin D1, cyclin D3, p27, p16, p21, CDK4, CDK2 and CDK1.

In conclusion, our study in hereditary breast cancer tumors analyzing 37 immunohistochemical markers, define the molecular differences between BRCA1 and BRCA2 tumors with respect to hormonal receptors, cell cycle, apoptosis and basal cell markers.

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Authors and Affiliations

  1. Breast and Gynaecological Cancer Laboratory, Centro Nacional de Investigaciones Oncológicas (CNIO), Madrid

    José Palacios & David Sarrió

  2. Department of Human Genetics, Centro Nacional Investigaciones Oncológicas (CNIO), Melchor Fernández Almagro, 3, 28029, Madrid, Spain

    Emiliano Honrado, Ana Osorio, Alicia Barroso, Sandra Rodríguez, Juan C. Cigudosa & Javier Benítez

  3. Department of Pathology, Fundación Jiménez Díaz, Universidad Autónoma, Madrid

    Alicia Cazorla & Carmen Rivas

  4. Cytogenetics Unit, Centro Nacional de Investigaciones Oncológicas (CNIO), Madrid

    Sandra Rodríguez & Juan C. Cigudosa

  5. Department of Genetics, Centro Nacional de Investigaciones Oncológicas (CNIO), Madrid

    Orland Diez

  6. Department of Oncology, Centro Nacional de Investigaciones Oncológicas (CNIO), Madrid

    Carmen Alonso

  7. Department of Pathology, Hospital de la Santa Creu i Sant Pau, Barcelona

    Enrique Lerma

  8. Bioinformatics Unit, Centro Nacional de Investigaciones Oncológicas (CNIO), Madrid, Spain

    Joaquín Dopazo

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  1. José Palacios
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  2. Emiliano Honrado
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  3. Ana Osorio
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  4. Alicia Cazorla
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  5. David Sarrió
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  6. Alicia Barroso
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  7. Sandra Rodríguez
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  8. Juan C. Cigudosa
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  9. Orland Diez
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  10. Carmen Alonso
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  11. Enrique Lerma
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  12. Joaquín Dopazo
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  13. Carmen Rivas
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  14. Javier Benítez
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Correspondence to Javier Benítez.

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Palacios, J., Honrado, E., Osorio, A. et al. Phenotypic characterization of BRCA1 and BRCA2 tumors based in a tissue microarray study with 37 immunohistochemical markers. Breast Cancer Res Treat 90, 5–14 (2005). https://doi.org/10.1007/s10549-004-1536-0

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