Expression of human epidermal growth factor receptor 2 (HER2) is an important biomarker in breast cancer patients who can benefit from cost-effective automatic Hematoxylin and Eosin (H&E) HER2 scoring. However, developing such scoring models requires large pixellevel annotated datasets. Transfer learning allows prior knowledge from different datasets to be reused while multiple-instance learning (MIL) allows the lack of detailed annotations to be mitigated. The aim of this work is to examine the potential of transfer learning on the performance of deep learning models pre-trained on (i) Immunohistochemistry (IHC) images, (ii) H&E images and (iii) non-medical images. A MIL framework with an attention mechanism is developed using pre-trained models as patch-embedding models. It was found that embedding models pre-trained on H&E images consistently outperformed the others, resulting in an average AUC-ROC value of 0.622 across the 4 HER2 scores (0.59 0.80 per HER2 score). Furthermore, it was found that using multiple-instance learning with an attention layer not only allows for good classification results to be achieved, but it can also help with producing visual indication of HER2-positive areas in the H&E slide image by utilising the patch-wise attention weights.

We developed a rapid scanning optical microscope, termed "BlurryScope", that leverages continuous image acquisition and deep learning to provide a cost-effective and compact solution for automated inspection and analysis of tissue sections. BlurryScope integrates specialized hardware with a neural network-based model to quickly process motion-blurred histological images and perform automated pathology classification. This device offers comparable speed to commercial digital pathology scanners, but at a significantly lower price point and smaller size/weight, making it ideal for fast triaging in small clinics, as well as for resourcelimited settings. To demonstrate the proof-of-concept of BlurryScope, we implemented automated classification of human epidermal growth factor receptor 2 (HER2) scores on immunohistochemically (IHC) stained breast tissue sections, achieving concordant results with those obtained from a high-end digital scanning microscope. We evaluated this approach by scanning HER2-stained tissue microarrays (TMAs) at a continuous speed of 5,000 µm/s, which introduces bidirectional motion blur artifacts. These compromised images were then used to train our network models. Using a test set of 284 unique patient cores, we achieved blind testing accuracies of 79.3% and 89.7% for 4-class (0, 1+, 2+, 3+) and 2-class (0/1+, 2+/3+) HER2 score classification, respectively. BlurryScope automates the entire workflow, from image scanning to stitching and cropping of regions of interest, as well as HER2 score classification. We believe BlurryScope has the potential to enhance the current pathology infrastructure in resource-scarce environments, save diagnostician time and bolster cancer identification and classification across various clinical environments.

Human epidermal growth factor receptor 2 (HER2) is a critical protein in cancer cell growth that signifies the aggressiveness of breast cancer (BC) and helps predict its prognosis. Accurate assessment of immunohistochemically (IHC) stained tissue slides for HER2 expression levels is essential for both treatment guidance and understanding of cancer mechanisms. Nevertheless, the traditional workflow of manual examination by board-certified pathologists encounters challenges, including inter- and intra-observer inconsistency and extended turnaround times. Here, we introduce a deep learning-based approach utilizing pyramid sampling for the automated classification of HER2 status in IHC-stained BC tissue images. Our approach analyzes morphological features at various spatial scales, efficiently managing the computational load and facilitating a detailed examination of cellular and larger-scale tissue-level details. This method addresses the tissue heterogeneity of HER2 expression by providing a comprehensive view, leading to a blind testing classification accuracy of 84.70%, on a dataset of 523 core images from tissue microarrays. Our automated system, proving reliable as an adjunct pathology tool, has the potential to enhance diagnostic precision and evaluation speed, and might significantly impact cancer treatment planning.

Supervised deep learning has shown state-of-the-art performance for medical image segmentation across different applications, including histopathology and cancer research; however, the manual annotation of such data is extremely laborious. In this work, we explore the use of superpixel approaches to compute a pre-segmentation of HER2 stained images for breast cancer diagnosis that facilitates faster manual annotation and correction in a second step. Four methods are compared: Standard Simple Linear Iterative Clustering (SLIC) as a baseline, a domain adapted SLIC, and superpixels based on feature embeddings of a pretrained ResNet-50 and a denoising autoencoder. To tackle oversegmentation, we propose to hierarchically merge superpixels, based on their content in the respective feature space. When evaluating the approaches on fully manually annotated images, we observe that the autoencoder-based superpixels achieve a 23% increase in boundary F1 score compared to the baseline SLIC superpixels. Furthermore, the boundary F1 score increases by 73% when hierarchical clustering is applied on the adapted SLIC and the autoencoder-based superpixels. These evaluations show encouraging first results for a pre-segmentation for efficient manual refinement without the need for an initial set of annotated training data.

The immunohistochemical (IHC) staining of the human epidermal growth factor receptor 2 (HER2) biomarker is widely practiced in breast tissue analysis, preclinical studies and diagnostic decisions, guiding cancer treatment and investigation of pathogenesis. HER2 staining demands laborious tissue treatment and chemical processing performed by a histotechnologist, which typically takes one day to prepare in a laboratory, increasing analysis time and associated costs. Here, we describe a deep learning-based virtual HER2 IHC staining method using a conditional generative adversarial network that is trained to rapidly transform autofluorescence microscopic images of unlabeled/label-free breast tissue sections into bright-field equivalent microscopic images, matching the standard HER2 IHC staining that is chemically performed on the same tissue sections. The efficacy of this virtual HER2 staining framework was demonstrated by quantitative analysis, in which three board-certified breast pathologists blindly graded the HER2 scores of virtually stained and immunohistochemically stained HER2 whole slide images (WSIs) to reveal that the HER2 scores determined by inspecting virtual IHC images are as accurate as their immunohistochemically stained counterparts. A second quantitative blinded study performed by the same diagnosticians further revealed that the virtually stained HER2 images exhibit a comparable staining quality in the level of nuclear detail, membrane clearness, and absence of staining artifacts with respect to their immunohistochemically stained counterparts. This virtual HER2 staining framework bypasses the costly, laborious, and time-consuming IHC staining procedures in laboratory, and can be extended to other types of biomarkers to accelerate the IHC tissue staining used in life sciences and biomedical workflow.

Evaluating expression of the Human epidermal growth factor receptor 2 (Her2) by visual examination of immunohistochemistry (IHC) on invasive breast cancer (BCa) is a key part of the diagnostic assessment of BCa due to its recognised importance as a predictive and prognostic marker in clinical practice. However, visual scoring of Her2 is subjective and consequently prone to inter-observer variability. Given the prognostic and therapeutic implications of Her2 scoring, a more objective method is required. In this paper, we report on a recent automated Her2 scoring contest, held in conjunction with the annual PathSoc meeting held in Nottingham in June 2016, aimed at systematically comparing and advancing the state-of-the-art Artificial Intelligence (AI) based automated methods for Her2 scoring. The contest dataset comprised of digitised whole slide images (WSI) of sections from 86 cases of invasive breast carcinoma stained with both Haematoxylin & Eosin (H&E) and IHC for Her2. The contesting algorithms automatically predicted scores of the IHC slides for an unseen subset of the dataset and the predicted scores were compared with the 'ground truth' (a consensus score from at least two experts). We also report on a simple Man vs Machine contest for the scoring of Her2 and show that the automated methods could beat the pathology experts on this contest dataset. This paper presents a benchmark for comparing the performance of automated algorithms for scoring of Her2. It also demonstrates the enormous potential of automated algorithms in assisting the pathologist with objective IHC scoring.