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Id4 protein is highly expressed in triple-negative breast carcinomas: possible implications for BRCA1 downregulation

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Abstract

BRCA1 germline mutation carriers usually develop ER, PR and HER2 negative breast carcinoma. Somatic BRCA1 mutations are rare in sporadic breast cancers, but other mechanisms could impair BRCA1 functions in these tumors, particularly in triple-negative breast carcinomas (TNBCs). Id4, a helix-loop-helix DNA binding factor, blocks BRCA1 gene transcription in vitro and could downregulate BRCA1 in vivo. We compared Id4 immunoreactivity in 101 TNBCs versus 113 non-TNBCs, and correlated the results with tumor morphology and immunoreactivity for CK5/6, CK14, EGFR, and androgen receptor (AR). Id4 was present in 76 out of 101 (75 %) TNBCs: 40 (40 %) TNBCs displayed Id4 positivity in >50 % of neoplastic cells, 23 (23 %) in 5–50 %, and 13 (13 %) in <5 %. In contrast, only 6 (5 %) of 113 non-TNBCs showed focal Id4 positivity, limited to fewer than 5 % of the tumor (p < 0.0001). Id4 expression significantly associated with high histologic grade (p = 0.0002) and mitotic rate (p = 0.006). Id4 decorated all 12 TNBCs with large central acellular zone of necrosis in our series, with positive staining in 10–90 % of the cells. Id4 signal strongly correlated with cytokeratin CK14 reactivity (p < 0.0001), but not with CK5/6 and EGFR. All apocrine carcinomas in our series were positive for AR and most for EGFR, but they were negative for CK5/6, CK14, and Id4, with only two exceptions. Our results document substantial expression of Id4 in most TNBCs, which could result in functional downregulation of BRCA1 pathways in these tumors.

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Disclosure

The authors declare that neither pharmaceutical nor industry support was provided for this work. No funding for this project was received from any of the following organizations: National Institutes of Health (NIH); Wellcome Trust; Howard Hughes Medical Institute (HHMI); or other(s).

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The authors declare no conflict of interest.

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Authors and Affiliations

  1. Department of Pathology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA

    Yong Hannah Wen, Muzaffar Akram, Jeff Catalano & Edi Brogi

  2. Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

    Alice Ho

  3. Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

    Sujata Patil & Anne Eaton

  4. Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

    Larry Norton

  5. Department of Cancer Biology and Genetics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

    Robert Benezra

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  1. Yong Hannah Wen
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Wen, Y.H., Ho, A., Patil, S. et al. Id4 protein is highly expressed in triple-negative breast carcinomas: possible implications for BRCA1 downregulation. Breast Cancer Res Treat 135, 93–102 (2012). https://doi.org/10.1007/s10549-012-2070-0

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