1635P - Comparison of the 2007 and 2013 ASCO/CAP guidelines for HER2 ISH testing in invasive breast cancer patients

Date 28 September 2014
Event ESMO 2014
Session Poster Display session
Topics Breast Cancer
Pathology/Molecular Biology
Basic Scientific Principles
Presenter Marta Salido
Citation Annals of Oncology (2014) 25 (suppl_4): iv564-iv573. 10.1093/annonc/mdu359
Authors M. Salido1, A. Puiggros1, J.M. Corominas2, M. Iglesias2, M. Rodriguez-Rivera1, C. Melero1, I. Tusquets Trias Bes3, J. Albanell3, S. Serrano2, S. Servitja Tormo3, B. Espinet1
  • 1Pathology Department. Molecular Cytogenetic Laboratory, Hospital del Mar, 08003 - Barcelona/ES
  • 2Pathology Department, Hospital del Mar, 08003 - barcelona/ES
  • 3Medical Oncology, University Hospital del Mar, 08003 - Barcelona/ES



The American Society of Clinical Oncology and the College of American Pathologists have issued joint updated comprehensive recommendations for human epidermal growth factor receptor 2 (HER2) testing in breast cancer. In relation to the in situ hybridization (ISH) scoring, HER2 positivity is redefined as HER2 copy number of ≥6.0 signals/cell, or HER2/CEP17 ratio of ≥2, instead of 2.2. The equivocal category includes cases with a copy number >4 to <6 signals/cell and a ratio of <2. Both copy number and ratio have to be considered without any evidence provided that supports these changes. The aim of our study was to compare the ISH criteria defined in the ASCO update (2013) with the previously reported (2007) in the routine practice.


A total of 430 FFPE breast tumor samples routinely analyzed between January 2013 and February 2014 were included. HER2 amplification was assessed by Silver In Situ Hybridization (SISH) technique (Ventana Medical Systems). Comparison between HER2 results according to 2007 and 2013 ASCO/CAP ISH recommendations was made.


Results are disclosed in table 1. In 59 out of 430 samples (13.7%) a discordant ISH result was found. In most of the cases (42/59; 71%) the result changed from negative to equivocal being 51% of them negative by IHC and 23% 2+ (ten cases were not assessable). Fourteen samples (14/59; 23.7%) became a new positive result; most of them (n=11) were equivocal cases with ≥6.0 signals/cell and ratio between 2 and 2.2. IHC of 9 out 11 of these cases did not show a positive result. Finally, only 3 equivocal cases became negative according to the new scoring (3/59; 5%).

Comparison of the overall ISH results

Number of Cases ASCO/CAP (Wolff et al., 2007) Number of cases ASCO/CAP (Wolff et al., 2013)
ISH Postitive 87 101
ISH Negative 322 280
ISH Equivocal 21 49


Using 2013 criteria we observed an increase in the number of inconclusive cases (4.8% vs. 11%), thus causing the need to repeat the ISH technique on another sample or if the result remains inconclusive to perform an alternative test. Most of these cases showed polysomy of chromosome 17 and were negative by IHC. An increase in the number of positive cases was also observed (20% vs. 23.4%). However, no correlation between new ISH criteria and IHC was observed.


All authors have declared no conflicts of interest.