1. Correlation of In Situ HER2 RNA Expression With HER2 Immunohistochemistry and Fluorescence In Situ Hybridization Categories in Breast Cancer
- Author
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Tseng, Yu-Fen, Li, Yu-Chia, Lee, Yi-Hsuan, Hu, Hsiang-We, Zhang, Man-San, Hung, Tze-Chun, and Lien, Huang-Chun
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Immunohistochemistry -- Health aspects ,RNA sequencing -- Health aspects ,Fluorescence -- Health aspects ,RNA -- Health aspects ,Chromosomes -- Health aspects ,Breast cancer -- Health aspects ,Epidermal growth factor -- Health aspects ,Health - Abstract
* Context.--RNA sequencing study has demonstrated that human epidermal growth factor receptor 2 (HER2) RNA levels influence anti-HER2 therapeutic efficacy. However, in situ HER2 RNA expression (isHRE), which evaluates HER2 RNA expression in tissue, has remained unclear in breast cancers (BCs) of various HER2 immunohistochemistry (IHC)/in situ hybridization (ISH) categories. Objective.--To correlate isHRE with all HER2 IHC/ fluorescence ISH (FISH) categories in BC. Design.--Formalin-fixed, paraffin-embedded tissue sections from 259 BCs, covering all IHC/FISH categories, were analyzed for isHRE by RNAscope. Results.--We validated HER2 RNAscope scoring as a semiquantitative method to evaluate isHRE and demonstrated significantly higher RNAscope scores in IHC 3+ than in IHC 2+ cases, and in IHC 2+ than in IHC 0/1 + cases. Among the 5 IHC 2+/FISH groups, group 1 (G1) cases had the highest scores. The scores in G3 cases were higher than those in G2, but not significantly different from those in G4 and G5. G4 cases had significantly higher scores than those in G2. Higher HER2 copy numbers and HER2:CEP 17 (centromere 17) copy number ratios were significantly correlated with higher isHRE in G1 cases, but not in G2 to G5 cases. RNAscope scores were significantly lower in HER2-negative (IHC 0) than in HER2-low (IHC 2+/FISH- and IHC 1+) BCs but were not different between IHC 0 and 1+ BCs when analyzed separately. Conclusions.--We demonstrate the HER2 RNA expression status among BCs of various HER2 IHC/FISH categories in tissue. Such information may be relevant for anti-HER2 treatment decisions considering the role of HER2 RNA expression in predicting anti-HER2 therapeutic efficacy., Approximately 15% of invasive breast cancers (BCs) are human epidermal growth factor receptor 2 (HER2) positive, defined as HER2 gene amplification or protein overexpression, (1) and such tumors are sensitive [...]
- Published
- 2024
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