Image Analysis of HER2 Immunohistochemical Staining Reproducibility and Concordance With Fluorescence In Situ Hybridization of a Laboratory-Validated Scoring Technique

Dept. of Laboratory Medicine and Pathology, Mayo Clinic, 200 First St SW, Rochester, MN 55905, USA.
American Journal of Clinical Pathology (Impact Factor: 2.51). 02/2012; 137(2):270-6. DOI: 10.1309/AJCP9MKNLHQNK2ZX
Source: PubMed


Image analysis of the HER2 immunohistochemical (IHC) stain can help determine which breast cancer patients may benefit from HER2-targeted therapy. We studied the concordance of HER2 IHC and fluorescence in situ hybridization (FISH) as well as reproducibility of surgical pathologist (SP) and cytotechnologist (CT) interpretations using manual and image analysis methodologies on 154 IHC cases. Concordances with FISH were good for IHC negative (0, 1+) cases (range, 97%-100%) and positive (3+) cases (range, 87%-100%). Image analysis had fewer equivocal (2+) results (10.4%) than CT (14.9%) and SP (16.2%) manual methods, with higher concordances to FISH (31%, 26%, and 20% for image analysis, CT manual, and SP manual, respectively). CT manual (κ = 0.747) and image analysis (κ = 0.779) methods had better interobserver reproducibility than SP manual (κ = 0.697). CT image analysis had better intraobserver reproducibility (κ = 0.882) than CT (κ = 0.828) and SP (κ = 0.766) manual methods. HER2 IHC analysis performed by image analysis can produce accurate results with improved reproducibility.

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Available from: Aziza Nassar, Aug 21, 2014
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    • "The levels of serum HER2 as well as tumor tissue HER2 have been detected to be increased in the patients with breast cancer [33]. In clinical practice,immunohistochemistry (IHC) and fluorescence in situ hybridisation (FISH) are the suggested methods to determine HER2 status in cancer specimens [33, 34]. Currently, FDA has approved several kits or assays of IHC or FISH to determine HER2 expression. "
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    Oncotarget 06/2014; 5(13). DOI:10.18632/oncotarget.2050 · 6.36 Impact Factor
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    ABSTRACT: Background: Prognostic and predictive tumor markers in breast cancer are most commonly performed on core needle biopsies (CNB) of the primary tumor. Because treatment recommendations are influenced by these markers, it is imperative to verify strong concordance between tumor markers on CNB specimens and the corresponding surgical specimens (SS). Study design: A prospective study was performed on 165 women (205 samples) with breast cancer diagnosed from January 2009 to July 2011. Tumor type, grade, estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor 2 (HER2), and Ki67 expression by immunohistochemical (IHC) testing were retrospectively analyzed in the CNB and SS. Contingency tables and agreement modeling were performed. Results: There was substantial agreement between the CNB and SS for PR% and HER2; moderate agreement for tumor type, grade, and ER%; and fair agreement for Ki67%. In 8% of patients (n = 13), tumor heterogeneity was seen. In heterogeneous tumors the overall concordance between the CNB and SS was worse, especially for HER2. Six of these patients had areas of tumor that were positive for HER2, which were not detected in their CNBs. Nine patients had multiple distinct molecular subtypes within their tumor(s). Conclusions: The heterogeneous distribution of antigens in breast cancer tumors raises concern that the CNB may not adequately represent the true biologic profile in all patients. There is strong concordance for tumor type, ER, and PR between CNB and SS (although a quantitative decline was noted from CNB to SS); however, HER2 activity does not appear to be adequately detected on CNB in patients with heterogeneous tumors. These data suggest that IHC testing on the CNB alone may not be adequate to tailor targeted therapy in all patients.
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