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FGFR1 copy number in breast cancer: associations with proliferation, histopathological grade and molecular subtypes
  1. Anna M Bofin1,
  2. Borgny Ytterhus1,
  3. Elise Klæstad1,
  4. Marit Valla1,2
  1. 1Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway
  2. 2Department of Pathology, St. Olav's Hospital, Trondheim University Hospital, Trondheim, Norway
  1. Correspondence to Professor Anna M Bofin, Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology Faculty of Medicine and Health Sciences, Trondheim 7491, Norway; anna.bofin{at}ntnu.no

Abstract

Aims FGFR1 is located on 8p11.23 and regulates cell proliferation and survival. Increased copy number of FGFR1 is found in several cancers including cancer of the breast. ZNF703 is located close to FGFR1 at 8p11-12 and is frequently expressed in the luminal B subtype of breast cancer. Using tissue samples from a well-described cohort of patients with breast cancer with long-term follow-up, we studied associations between FGFR1 copy number in primary breast cancer tumours and axillary lymph node metastases, and proliferation status, molecular subtype and prognosis. Furthermore, we studied associations between copy number increase of FGFR1 and copy number of ZNF703.

Methods We used fluorescence in situ hybridisation for FGFR1 and the chromosome 8 centromere applied to tissue microarray sections from a series of 534 breast cancer cases.

Results We found increased copy number (≥4) of FGFR1 in 74 (13.9%) of tumours. Only 6 of the 74 cases with increased copy number were non-luminal. Increased FGFR1 copy number was significantly associated with high Ki-67 status, high mitotic count and high histopathological grade, but not with prognosis. Forty-two (7.9%) cases had mean copy number ≥6. Thirty of these showed ZNF708 copy number ≥6.

Conclusions Our results show that FGFR1 copy number increase is largely found among luminal subtypes of breast cancer, particularly luminal B (HER2). It is frequently accompanied by increased copy number of ZNF703. FGFR1 copy number increase is associated with high histopathological grade and high proliferation. However, we did not discover an association with prognosis.

  • pathology
  • molecular
  • genes
  • neoplasm
  • breast neoplasms

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Footnotes

  • Handling editor Runjan Chetty.

  • Contributors AMB: conception and design; analysis and interpretation of data; drafting the article; final approval. BY: acquisition of data; final approval. EK: analysis and interpretation of data; final approval. MV: analysis and interpretation of data; drafting the article; final approval.

  • Funding The study was funded by the Liaison Committee for Education, Research and Innovation in Central Norway, The Central Norway Health Authority. Grant number: 46030001.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Ethics approval This study was approved by the Regional Committee for Medical and Health Research Ethics, Central Norway. Approval number: REK 836-09. The approval of this study includes dispensation from the general requirement of patient consent.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data are available upon reasonable request. The datasets included in the current study are not publicly available but are available from the corresponding author on reasonable request.

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