Using Whole Slide Gray Value Map to Predict HER2 Expression and FISH Status in Breast Cancer

SIMPLE SUMMARY: HER2 expression is important for target therapy in breast cancer patients, however, accurate evaluation of HER2 expression is challenging for pathologists owing to the ambiguities and subjectivities of manual scoring. We proposed a deep learning framework using a Whole Slide gray value map and convolutional neural network model to predict HER2 expression level on immunohistochemistry (IHC) assay and predict HER2 gene status on fluorescence in situ hybridization (FISH) assay. Our results indicated that the proposed model is feasible for predicting HER2 expression and gene amplification and achieved high consistency with the experienced pathologists’ assessment. This unique HER2 scoring model did not rely on challenging manual intervention and proved to be a simple and robust tool for pathologists to improve the accuracy of HER2 interpretation and provided a clinical aid to target therapy in breast cancer patients. ABSTRACT: Accurate detection of HER2 expression through immunohistochemistry (IHC) is of great clinical significance in the treatment of breast cancer. However, manual interpretation of HER2 is challenging, due to the interobserver variability among pathologists. We sought to explore a deep learning method to predict HER2 expression level and gene status based on a Whole Slide Image (WSI) of the HER2 IHC section. When applied to 228 invasive breast carcinoma of no special type (IBC-NST) DAB-stained slides, our GrayMap+ convolutional neural network (CNN) model accurately classified HER2 IHC level with mean accuracy 0.952 ± 0.029 and predicted HER2 FISH status with mean accuracy 0.921 ± 0.029. Our result also demonstrated strong consistency in HER2 expression score between our system and experienced pathologists (intraclass correlation coefficient (ICC) = 0.903, Cohen’s κ = 0.875). The discordant cases were found to be largely caused by high intra-tumor staining heterogeneity in the HER2 IHC group and low copy number in the HER2 FISH group.