Article Text

Download PDFPDF
Predictors of human epidermal growth factor receptor 2 fluorescence in-situ hybridisation amplification in immunohistochemistry score 2+ infiltrating breast cancer: a single institution analysis
  1. Maria Vittoria Dieci1,
  2. Elena Barbieri1,
  3. Stefania Bettelli2,
  4. Federico Piacentini1,
  5. Claudia Omarini1,
  6. Guido Ficarra2,
  7. Sara Balduzzi1,
  8. Massimo Dominici1,
  9. Pierfranco Conte1,
  10. Valentina Guarneri1
  1. 1Department of Oncology, Hematology and Respiratory Diseases, University Hospital, Modena, Italy
  2. 2Department of Pathology, University Hospital, Modena, Italy
  1. Correspondence to Dr Maria Vittoria Dieci, Department of Oncology, Hematology and Respiratory Diseases, University Hospital, via del Pozzo 71, Modena 41124, Italy; vitti10{at}


Aims Eligibility for anti-human epidermal growth factor receptor 2 (HER2) treatments in breast cancer requires a correct HER2 status assessment. Testing guidelines recommend fluorescence in-situ hybridisation (FISH) for samples scored as 2+ by immunohistochemistry. This study investigates the correlation between pathological features and FISH amplification in HER2 2+ breast cancer cases.

Methods 480 HER2 2+ breast cancer samples were included. The association between tumour grade, hormone receptor status, proliferation index (Ki67) and FISH amplification, using both US Food and Drug Administration (ratio ≥2) and American Society of Clinical Oncologists/College of American Pathologists cut-offs (ratio >2.2) was evaluated.

Results 90.2% of the samples were hormone receptor positive. The median Ki67 value was 23.5%; 311 (64.8%) samples showed a Ki67 value of 15% or greater. Tumour grade was evaluable in 421 cases (87.7%), 268 (55.8%) being grade 3. FISH amplification rates were 27.5% (ratio ≥2.0) and 20.8% (ratio >2.2). Grade 3 tumours were more frequently amplified than grades 1–2 tumours: 34% versus 18% (ratio ≥2.0, p<0.001) and 27% versus 9% (ratio >2.2, p<0.001). Samples with Ki67 of 15% or greater showed higher amplification rates than low Ki67 samples: 31% versus 21% (ratio ≥2.0, p=0.022) and 25% versus 12% (ratio >2.2, p=0.003). The OR for FISH amplification was significant in the case of grade 3 and high Ki67 with both cut-offs.

Conclusions In this study, high tumour grade and high Ki67 significantly predicted FISH amplification in 480 HER2 2+ breast cancer samples.

  • Breast cancer
  • CERB 2
  • cervical cancer
  • FISH amplification
  • HER2
  • HPV
  • molecular oncology
  • proliferation
  • tumour grade

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.


  • Competing interests None declared.

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