[287] High Concordance between HercepTest IHC and HER2 FISH: An Analysis of Two Companion Diagnostic Tests before and after Implementation of ASCO/CAP 2007 Guidelines

Maria E Vergara-Lluri, Neda A Moatamed, Sophia K Apple. David Geffen UCLA Medical Center, Los Angeles, CA

Background: Human epidermal growth factor receptor 2 (HER2) is a critical predictive marker in patients with invasive breast cancer who can benefit from treatment with trastuzumab. It is thus imperative to ensure accuracy and precision in HER2 testing. In 2007, The American Society of Clinical Oncology/College of American Pathologists ASCO/CAP guidelines proposed new recommendations for HER2 testing for IHC and FISH scoring in an effort to improve accuracy and utility of these companion diagnostic tests as a predictive marker for patients with invasive breast cancer. The goal of the new guidelines was to improve the concordance rate between the diagnostic tests for HER2 and decrease the number of inconclusive cases.
Design: Both IHC and HER2 FISH were performed on all specimens from our facility from years 2003 through 2011 (n=1447). Cases from 2003 to 2007 (n=958) were scored by FDA guidelines prior to publication of ASCO/CAP guidelines, with IHC 3+ cases staining >10% of tumor cells and FISH amplification cutoff value of 2.0. The new ASCO/CAP guidelines were implemented and scored accordingly for cases from 2008 to 2011 (n=489), with IHC 3+ cases staining >30% of tumor cells and FISH amplification cutoff value of 2.2. We compared the concordance rates before and after ASCO/CAP guidelines to see if ASCO/CAP guidelines yielded improvement in concordance rate between IHC and FISH.

HER2 Immunohistochemical Status vs HER2 Gene Status by FISH
2003-2007  2008-2011 
IHCFISH -FISH +FISH -FISH +
029921343
1403182568
271473713
30118236
Total77318542960



Results: For the 2003-2007 study population, the concordance between the IHC and FISH HER2 assays was 93.3% with a kappa coefficient of 0.79. When the equivocal IHC 2+ cases were excluded from the analysis (n=118; 12% of cases), the agreement increased to 97.6% with a kappa coefficient of 0.91. For the 2008-2011 study population, the concordance between the two assays was 94.7% with a kappa coefficient of 0.71. When the equivocal immunohistochemical 2+ cases were excluded from the analysis (n=50; 10% of cases), the agreement increased to 97.0% with a kappa coefficient of 0.83. Comparison of kappa coefficients between cases scored in 2003-2007 versus 2008-2011, k=0.91 vs k=0.83, did not show a significant difference.
Conclusions: In our study, implementation of the new ASCO/CAP HER2 scoring guidelines did not show a significant difference in concordance rates and did not decrease the number of inconclusive cases in specimens.
Category: Breast

Tuesday, March 20, 2012 9:15 AM

Platform Session: Section B, Tuesday Morning

 

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