Breast Cancer Research and Treatment

, Volume 162, Issue 2, pp 243–253 | Cite as

FGD5 amplification in breast cancer patients is associated with tumour proliferation and a poorer prognosis

  • Marit Valla
  • Monica Jernberg Engstrøm
  • Borgny Ytterhus
  • Åse Kristin Skain Hansen
  • Lars Andreas Akslen
  • Lars Johan Vatten
  • Signe Opdahl
  • Anna Mary Bofin
Preclinical study



Proliferation is a hallmark of cancer. Using a combined genomic approach, FGD5 amplification has been identified as a driver of proliferation in Luminal breast cancer. We aimed to describe FGD5 copy number change in breast cancer, and to assess a possible association with tumour proliferation and prognosis.


We used fluorescence in situ hybridization targeting FGD5 and chromosome 3 centromere (CEP3) on formalin-fixed, paraffin-embedded tissue from 430 primary breast cancers and 108 lymph node metastases, from a cohort of Norwegian breast cancer patients. We tested the association between FGD5 copy number status and proliferation (assessed by Ki67 levels and mitotic count) using Pearson’s Chi square test, and assessed the prognostic impact of FGD5 copy number change by estimating cumulative risks of death and hazard ratios.


We identified FGD5 amplification (defined as FGD5/CEP3 ratio ≥2 or mean FGD5/tumour cell ≥4) in 9.5% of tumours. Mitotic count and Ki67 levels were higher in tumours with FGD5 copy number increase, compared to tumours with no copy number change. After 10 years of follow-up, cumulative risk of death from breast cancer was higher among cases with FGD5 amplification [48.1% (95% CI 33.8–64.7)], compared to non-amplified cases [27.7% (95% CI 23.4–32.6)].


FGD5 is a new prognostic marker in breast cancer, and increased copy number is associated with higher tumour proliferation and poorer long-term prognosis.


Breast cancer FGD5 FISH Gene amplification Proliferation Prognosis 



The authors thank the Department of Pathology and Medical Genetics at St. Olav’s Hospital, Trondheim University Hospital, Norway for making the archives available for the study; the Cancer Registry of Norway, and the Norwegian Cause of Death Registry for providing the patient data, and Hong Yan Dai for assistance in the design of the FGD5 probe used in this study. This work was supported by the Research Council of Norway (Project No. 231297); and the Liaison Committee between the Central Norway Regional Health Authority and the Norwegian University of Science and Technology (Project Nos. 46030001 and 46056705).

Compliance with ethical standards

Ethical standards

The study was approved by the Regional Committee for Medical and Health Sciences Research Ethics (REK, Midt-Norge, Norway, reference number 836/2009).

Conflicts of interest

The authors declare that they have no conflicts of interest.

Supplementary material

10549_2017_4125_MOESM1_ESM.docx (24 kb)
Supplementary material 1 (DOCX 25 kb)


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Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Marit Valla
    • 1
  • Monica Jernberg Engstrøm
    • 1
    • 2
  • Borgny Ytterhus
    • 3
  • Åse Kristin Skain Hansen
    • 3
  • Lars Andreas Akslen
    • 4
    • 5
  • Lars Johan Vatten
    • 1
  • Signe Opdahl
    • 1
  • Anna Mary Bofin
    • 3
  1. 1.Department of Public Health and General Practice, Faculty of MedicineNorwegian University of Science and TechnologyTrondheimNorway
  2. 2.Department of Breast and Endocrine Surgery, St. Olav’s HospitalTrondheim University HospitalTrondheimNorway
  3. 3.Department of Laboratory Medicine, Children’s and Women’s Health, Faculty of MedicineNorwegian University of Science and TechnologyTrondheimNorway
  4. 4.Department of Clinical Medicine, Centre for Cancer Biomarkers CCBIOUniversity of BergenBergenNorway
  5. 5.Department of PathologyHaukeland University HospitalBergenNorway

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