High Concordance Between Herceptest Immunohistochemistry and ERBB2 Fluorescence in Situ Hybridization Before and After Implementation of American Society of Clinical Oncology/College of American Pathology 2007 Guidelines

Maria E Vergara-Lluri; Neda A Moatamed; Elizabeth Hong; Sophia K Apple

Disclosures

Mod Pathol. 2012;25(10):1326-1332. 

In This Article

Abstract and Introduction

Abstract

Human epidermal growth factor receptor 2 (HER2, ERBB2) is an important critical predictive marker in patients with invasive breast cancer. It is thus imperative to ensure accuracy and precision in HER2 and ERBB2 testing. In 2007, the American Society of Clinical Oncology and College of American Pathologists (ASCO/CAP) proposed new guidelines for immunohistochemistry and fluorescence in-situ hybridization scoring in an effort to improve accuracy and utility of these companion diagnostic tests. The goal of the 2007 guidelines was to improve concordance rates between the diagnostic tests and decrease the number of inconclusive cases. This study examines the impact in concordance rates and number of inconclusive cases based on the recent change in guidelines in a large study cohort. HER2 immunohistochemistry and ERBB2 fluorescence in-situ hybridization were performed on all specimens from our facility from years 2003 through 2010 (n=1437). Cases from 2003–2007 (n=1016) were scored using Food and Drug Administration guidelines, with immunohistochemical 3+ cases staining >10% of tumor cells and fluorescence in-situ hybridization amplification cutoff value of 2.0. The 2007 guidelines were implemented and scored accordingly for cases from 2008–2010 (n=421), with immunohistochemical 3+ cases staining >30% of tumor cells and fluorescence in-situ hybridization amplification cutoff value of 2.2. We compared concordance rates before and after 2007 guidelines. For the 2003–2007 study population, the concordance rate between the assays was 97.6% with a corresponding kappa coefficient (k) of 0.90. For the 2008–2010 study population, concordance rate was 97.6% with a corresponding k of 0.89. There was no significant difference in number of inconclusive rates before and after 2007 guidelines. In our study, implementation of the new ASCO/CAP 2007 HER2 guidelines did not show a significant difference in concordance rates and did not decrease the number of inconclusive cases.

Introduction

Human epidermal growth factor receptor 2 gene, ERBB2 (frequently referred to as HER2), is a proto-oncogene located on chromosome 17, with a resultant 185-kDa glycoprotein. HER2 protein overexpression was initially recognized as a prognostic marker of poor clinical outcome.[1–3] This is characterized by amplification of the ERBB2 gene and accompanied by abnormally high levels of the glycoprotein.[4,5]

The discovery of trastuzumab (Herceptin), a monoclonal antibody to HER2 for the treatment of HER2-positive breast cancer, heralded the additional significance of HER2 as a critical predictive marker in patients with invasive breast cancer who can benefit from this therapy.[3] Studies have validated the efficacy of trastuzumab in HER2-positive breast cancer in both adjuvant and metastatic settings.[6–8] Furthermore, HER2 overexpression has been found to confer a relative resistance to endocrine therapies.[9] Thus, the accurate assessment of HER2 status is essential in the clinical treatment algorithm for patients with breast cancer.

In 2007, the American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) proposed new recommendations for HER2 immunohistochemistry and ERBB2 fluorescence in-situ hybridization scoring in an effort to improve accuracy of these companion diagnostic tests as a predictive marker for patients with invasive breast cancer.[10] The goal of the new guidelines was to improve the concordance rate between the diagnostic tests for HER2 and to decrease the number of inconclusive cases.

Several publications have focused on the concordance rates between HER2 immunohistochemistry and ERBB2 fluorescence in-situ hybridization analysis, concentrating mainly on the analysis of different methods and the level of agreement between ERBB2-testing platforms.[11–14] At our institution, all cases of patients with invasive breast carcinoma undergo both HER2 immunohistochemical staining and ERBB2 gene fluorescence in-situ hybridization testing. The objective of this study is to assess the impact of ASCO/CAP 2007 guidelines on HER2 concordance rates and number of inconclusive cases in a single large institution.

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