Breast Cancer Research and Treatment

, Volume 127, Issue 3, pp 831–839 | Cite as

EMSY and CCND1 amplification in familial breast cancer: from the Ontario site of the Breast Cancer Family Registry

  • Anita L. BaneEmail author
  • Anna Marie Mulligan
  • Dushanthi Pinnaduwage
  • Frances P. O’Malley
  • Irene L. Andrulis
Brief Report


EMSY is a putative oncogene amplified in a minority of breast carcinomas, its protein product interacts with and transcriptionally silences BRCA2. We hypothesized that breast tumors from BRCA2 mutation carriers would be less likely than other familial breast cancers to exhibit EMSY amplification. As EMSY is located on 11q13 in proximity to CCND1, an established breast cancer oncogene, we also examined the amplification of CCND1 in the same tumor cohort. Amplification of EMSY and CCND1 were examined in 58 BRCA1-associated, 64 BRCA2-associated, and 242 familial non-BRCA1/BRCA2 breast cancers using fluorescent in situ hybridization (FISH). All tumors had a centralized pathology review and underwent molecular phenotyping by immunohistochemical profiling on tissue microarrays (TMAs). Tumors with amplification of EMSY and/or CCND1 were compared with non-amplified tumors for morphological appearance, molecular subtype, and overall survival. EMSY amplification was detected in 8% of BRCA1-associated, 0% of BRCA2-associated, and 9% of familial non-BRCA1/BRCA2 breast tumors (P = 0.036). CCND1 was amplified in 4% of BRCA1-associated, 13% of BRCA2-associated and 21% of non-BRCA1/BRCA2 breast tumors (P = 0.054). EMSY was amplified independently of CCND1 in 38% of cases. EMSY amplification was associated with increased tumor stage only; whereas CCND1 amplification was associated with high tumor grade, ER positivity, and inversely associated with the basal-like phenotype. There was a trend toward worse overall survival in ER-positive non-BRCA1/BRCA2 familial breast cancer patients whose tumors exhibited EMSY and CCND1 co-amplification. BRCA2-associated breast tumors are less likely than non-BRCA1/BRCA2 familial breast cancers to exhibit EMSY amplification. BRCA1-associated breast cancers are less likely than non-BRCA1/BRCA2 familial breast cancers to exhibit CCND1 amplification. EMSY amplification does occur independently of CCND1 amplification in a minority of familial breast cancers, supporting its role as a possible breast cancer oncogene.


Familial breast cancer EMSY amplification CCND1 amplification 



We thank the participants and staff of the Ontario site of the Breast Cancer Family Registry. This work was supported by the Canadian Breast Cancer Foundation and the National Cancer Institute under RFA-CA-06-503 and through cooperative agreements with members of the Breast Cancer Family Registry and Principal investigators, including Cancer Care Ontario (U01 CA69467). The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the Breast Cancer Family Registry, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government or the Breast Cancer Family Registry. This work was also supported by the Ontario Institute of Cancer Research.


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Copyright information

© Springer Science+Business Media, LLC. 2011

Authors and Affiliations

  • Anita L. Bane
    • 1
    • 2
    • 3
    Email author
  • Anna Marie Mulligan
    • 4
    • 5
  • Dushanthi Pinnaduwage
    • 6
  • Frances P. O’Malley
    • 4
    • 5
  • Irene L. Andrulis
    • 5
    • 6
    • 7
  1. 1.Department of Pathology and Molecular MedicineMcMaster UniversityHamiltonCanada
  2. 2.Department of OncologyMcMaster UniversityHamiltonCanada
  3. 3.Department of Pathology, Rm 2F-211Juravinski Hospital & Cancer CentreHamiltonCanada
  4. 4.Department of Laboratory MedicineSt. Michael’s HospitalTorontoCanada
  5. 5.Laboratory Medicine and PathobiologyUniversity of TorontoTorontoCanada
  6. 6.Samuel Lunenfeld Research InstituteMount Sinai HospitalTorontoCanada
  7. 7.Department of Molecular GeneticsUniversity of TorontoTorontoCanada

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