Effect of Normal Gand Staining on Amplification Results by FISH in HER2/Neu 3+ Invasive Carcinoma of the Breast
Faysal A Fedda, Chantal G Farra, Ayman N Tawil, Arafat Tfayli, Fouad I Boulos. American University of Beirut Medical Center, Beirut, Lebanon
Background: Although epithelial cells of normal ducts do not have HER2 gene amplification and should show essentially no levels of membrane staining by HER2 immunohistochemistry (IHC), HER2 staining in benign breast epithelium is occasionally encountered. The significance of this occurrence has not yet been substantially studied in the literature. It was however briefly addressed by the ASCO/CAP who recommended avoiding interpretation of IHC results in cancers with “strong staining of normal breast ducts”. The ASCO/CAP guidelines did not however provide a clear definition for “strong staining”, rendering it a largely subjective assessment. An alternative approach advocated by some authorities has been to subtract the amount of staining observed in normal breast epithelium from the score observed in breast cancer cells in the same section. The purpose of this study is to assess the correlation between HER2 IHC 3+ cases with normal gland staining (NGS) and their corresponding FISH results, to better understand the significance of such a finding on the final HER2 amplification status in carcinomas of the breast.
Design: 154 breast cancers cases with HER2 reported as positive (3+) between January 2005 and March 2011 were reviewed and HER2 status reconfirmed according to ASCO/CAP guidelines of 2007. NGS and other clinicopathologic characteristics were recorded. NGS was scored according to the same criteria used to score invasive cancer. Cases with 3+ HER2 status and NGS of at least 1+ were sent for FISH testing. Thirteen randomly selected positive controls without NGS were also sent for FISH confirmation.
Results: All patients were females with a median age at diagnosis of 55.5 years. Approximately 22% of cases (34/154) showed NGS for HER2. Twenty-four cases (70%) were grade 3, 9 (26%) were grade 2, and 1 (4%) was grade 1. FISH results were as follows: 67% (23/34) were confirmed as positive, 26% (9/34) were negative for amplification, and 6% (2/34) failed FISH testing. All 13 control cases tested positive by FISH. Of the 9 negative cases, four were grade 3, four grade 2, and one was grade 1.
Conclusions: Although based on a small cohort of samples, our study sheds light on an insufficiently studied phenomenon and highlights both its relatively high prevalence and association with significant discordance between IHC and FISH results. We therefore suggest careful assessment for NGS in all HER2 3+ cases, regardless of intensity and extent, and advocate a low threshold for FISH confirmation in such cases.
Wednesday, March 21, 2012 9:30 AM
Poster Session V # 45, Wednesday Morning