Assessment of dual-probe Her-2 fluorescent in situ hybridization in breast cancer by the 2013 ASCO/CAP guidelines produces more equivocal results than that by the 2007 ASCO/CAP guidelines

Abstract

Dual-probe fluorescence in situ hybridization (D-FISH) is a widely accepted method to determine the gene amplification status of human epidermal growth factor receptor 2 (Her-2). In 2013, the American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) updated the guidelines on the Her-2 testing for invasive breast cancer (BCa). The interpretation criteria for D-FISH changed accordingly. In this study, we compared the Her-2 FISH statuses based on the 2013 and 2007 ASCO/CAP guidelines in 1931 cases of BCa with Her-2 D-FISH testing at our hospital. We analyzed the clinicopathologic features of cases with equivocal results by the 2013 ASCO/CAP guidelines. Although the guideline update significantly improved the detection rate of Her-2 amplification, it also significantly increased the rate of equivocal results, posing a dilemma for clinical management. The equivocal results had good reproducibility. The distribution of D-FISH equivocal cases did not correlate with Her-2 status by immunohistochemistry, suggesting that Her-2 D-FISH equivocality may not reflect Her-2 overexpression. Compared with Her-2 negative cases by D-FISH, Her-2 D-FISH equivocal cases had higher Ki-67 expression, higher histological grade, more frequent lymph node metastasis, and lower estrogen receptor α expression, indicating a group of BCa with worse prognosis. The clinical significance of Her-2 equivocal results by D-FISH warrants further investigation.

High concordance of a closed-system, RT-qPCR breast cancer assay for HER2 mRNA, compared to clinically determined immunohistochemistry, fluorescence in situ hybridization, and quantitative immunofluorescence

“…For IHC this may be due to its semi-quantitative nature and non-standardized methods. FISH is thought by some to provide a more accurate assessment for HER2 status [ 7 , 8 ] since a chromosome count can be done, but the weakness of this method is that it does not necessarily reflect target protein expression [ 9 , 10 ] and counting FISH spots is tedious and biased by tumor heterogeneity [ 11 ]. Historically, slide-based measurements of mRNA have been tested, including using several commercially available platforms [ 12 – 14 ], but have not gained broad acceptance for assessment of HER2.…”

Diagnostic and prognostic values of contrast‑enhanced ultrasound combined with diffusion‑weighted magnetic resonance imaging in different subtypes of breast cancer

“…IHC was performed to detect the expression of estrogen receptor (ER) and progesterone receptor (PR) in BC tissues taken from patients included in the current study. The expression of Her-2 was measured based on the Recommendations for Human Epidermal Growth Factor Receptor 2 Testing in BC ( 20 ). Tissues were sent to the pathology department ≤30 min following collection.…”

Dasatinib inhibits c-src phosphorylation and prevents the proliferation of Triple-Negative Breast Cancer (TNBC) cells which overexpress Syndecan-Binding Protein (SDCBP)

“…TNBC samples were collected from consecutive breast cancer cases from January 2014 to February 2014, as described in our previous study [ 35 ]. The immunohistochemistry experiment was conduced in December 2014.…”