Assessment of HER2 status in breast cancer: overall positivity rate and accuracy by fluorescence in situ hybridization and immunohistochemistry in a single institution over 12 years: a quality control study

Zsuzsanna Varga,Holger Moch,Constanze Ramach,Aurelia Noske,Barbara Padberg

doi:10.1186/1471-2407-13-615

Zsuzsanna Varga, Holger Moch + Show 3 more

Open Access

https://doi.org/10.1186/1471-2407-13-615

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Abstract

BackgroundThe gold standard of HER2 status assessment in breast cancer is still debated. Immunohistochemistry (IHC) and in-situ technology as fluorescent-labeled methodology (FISH) can be influenced by pre-analytical factors, assay-conditions and interpretation of test results. We retrospectively conducted this quality control study and analyzed HER2 test results in breast cancer within the routine diagnostic service in a single institution over a period of 12 years. We addressed the question how stable and concordant IHC and FISH methods are and whether HER2 positivity rate has changed over this period.MethodsData of 7714 consecutive HER2-FISH-assays in a period of 12 years (2001–2012) on breast cancer biopsies and excision specimens were retrospectively analyzed. From 2001 to 2004, FISH tests were performed from all cases with IHC score 3+ and 2+ (and in some tumors with IHC score 1+ and 0). From 2005–2010, HER2 status was only determined by FISH. From 2011–2012, all breast carcinomas were analyzed by both IHC and FISH. Scoring and cut-off-definition were done according to time-current ASCO-CAP and FDA-guidelines.ResultsBetween 2001–2004, IHC score 3+ was diagnosed in 22% of cases, 69% of these 3+ cases were amplified by FISH. 6% of IHC score 0/1+ cases were amplified by FISH. There was a mean amplification rate of 15.8% (range 13 -19%) using FISH only HER2-assays (2005–2010). Starting 2008, a slight drop in the amplification rate from 17% to 14% was noticed due to the modified ASCO-criteria in 2007. From 2011–2012, 12% of cases were 3+ by IHC, 84% of them were amplified by FISH. Less than 1% of IHC score 0/1+ cases were amplified by FISH. Concordance between FISH and IHC increased from 83% to 97%.ConclusionsOur quality control study demonstrates that HER2 positivity rate remained stable by FISH-technology but showed a significant variation by IHC over the analyzed 12 years. Improvement in concordance rate was due to standardization of pre-analytical factors, scoring and interpretation.

Highlights

The gold standard of Human epidermal growth factor receptor 2 (HER2) status assessment in breast cancer is still debated
Patient collective The databank on HER2 Fluorescence in situ hybridization (FISH) testing in breast cancer of the Institute of Surgical Pathology, University Hospital Zurich, Switzerland was retrospectively analyzed in a 12 years period (2001–2012)
In this study we demonstrate that concordance-rate between IHC and FISH HER2 status in breast cancer significantly improved over 12 consecutive years and FISH only HER2 testing resulted in a constant amplification-rate

Summary

Introduction

Immunohistochemistry (IHC) and in-situ technology as fluorescent-labeled methodology (FISH) can be influenced by pre-analytical factors, assay-conditions and interpretation of test results. We retrospectively conducted this quality control study and analyzed HER2 test results in breast cancer within the routine diagnostic service in a single institution over a period of 12 years. The FDA approved methodologies include the assessment of the protein level by immunohistochemistry (IHC) or gene copy count on the DNA level by in situ hybridization technology (ISH) [2,3,4,5]. ASCO/CAP guidelines include the achievement of a concordance level of at least 95% for both positive and negative tumors when using IHC and ISH technology [3,5,6]. Economic issues of cost-effectiveness of IHC or ISH as primary test have been the issue of several previous studies and are still debated [10,11]

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