Is HER2 amplification predictable by digital immunohistochemistry?

Tamás Micsik,László Krecsák,Béla Molnár,Daniel Szabó,Tibor Krenács,Gábor Kiszler

doi:10.1186/1746-1596-8-s1-s14

Tamás Micsik, László Krecsák + Show 4 more

Open Access

https://doi.org/10.1186/1746-1596-8-s1-s14

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Abstract

HER2 positive breast cancers can benefit from trastuzumab therapy based on a validated immunohistocemical reports. HER2-negative and strong positive cases are easy to interpret, but equivocal cases should be analyzed with FISH-technique to reveal HER2 amplification. Image analysis methods have been recently developed such as MembraneQuant by 3DHISTECH to support this process. We validated MembraneQuant software on HER2-immunostained (clone 4B5) tissue microarrays of 100 breast cancers covering all positivity groups and tested if semi-automated software analysis of HER2 immunostaining can discriminate between FISH-positive and negative equivocal cases. The renowned 4-tiered evaluation guidelines were used. The HER2 gene status of the 15 equivocalcases was also assessed with FISH. Detailed MembraneQuant analysis in the 9 FISH- and 6 FISH+ cases was used to predict HER2 amplification status.

Highlights

In the last decade anti-HER2 treatment became one of the best examples for targeted treatment
Patients We selected invasive breast cancers from year 2002-to 2005 from the archive of the 1st Department of Pathology and Experimental Cancer Research of the Semmelweis University, Budapest, Hungary. 100 invasive ductal carcinomas were used in TMAs of 2mm cores of formalin-fixed paraffin embedded breast cancer specimens from females aged 26-86 years
TMA slides were used for HER2 IHC according to manufacturer’s protocol on a Bond-maxTM fully automated staining system (Leica Microsystems GmbH, Germany), using PATHWAY® HER-2/neu, whereas their duplicates were used for HER2-FISH testing by the Rembrandt Her2/Neu - Cen 17 FISH kit

Summary

Introduction

In the last decade anti-HER2 treatment became one of the best examples for targeted treatment. According to a four-tiered classification of international clinical guidelines, cases with strong and complete staining (IHC 3+) with anti-HER2 antibodies are eligible for trastuzumab therapy. The cases with complete, but moderate anti-HER2 stainings (2+ or equivocal) should be further investigated with (F) ISH-technique to determine HER2-amplification [1]. Negative and IHC 3+ cases are easy to interpret semiquantitatively on routine immunohistology, it is hard to conclude on the equivocal cases, sill, anti-HER2 therapy is indicated upon the predictive pathology report of HER2-expression and interobserver variability of IHCinterpretation still remains rather high [2]. The rapidly developing digital pathology solutions have promised better ways of archiving, documenting and standardizing immunohistochemistry including image analysis of HER2 detection to improve the efficacy of targeted anti-HER2 therapy [4]

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