Predicting the HER2 status in oesophageal cancer from tissue microarrays using convolutional neural networks.


Journal

British journal of cancer
ISSN: 1532-1827
Titre abrégé: Br J Cancer
Pays: England
ID NLM: 0370635

Informations de publication

Date de publication:
03 2023
Historique:
received: 13 05 2022
accepted: 05 01 2023
revised: 21 12 2022
medline: 30 3 2023
pubmed: 31 1 2023
entrez: 30 1 2023
Statut: ppublish

Résumé

Fast and accurate diagnostics are key for personalised medicine. Particularly in cancer, precise diagnosis is a prerequisite for targeted therapies, which can prolong lives. In this work, we focus on the automatic identification of gastroesophageal adenocarcinoma (GEA) patients that qualify for a personalised therapy targeting epidermal growth factor receptor 2 (HER2). We present a deep-learning method for scoring microscopy images of GEA for the presence of HER2 overexpression. Our method is based on convolutional neural networks (CNNs) trained on a rich dataset of 1602 patient samples and tested on an independent set of 307 patient samples. We additionally verified the CNN's generalisation capabilities with an independent dataset with 653 samples from a separate clinical centre. We incorporated an attention mechanism in the network architecture to identify the tissue regions, which are important for the prediction outcome. Our solution allows for direct automated detection of HER2 in immunohistochemistry-stained tissue slides without the need for manual assessment and additional costly in situ hybridisation (ISH) tests. We show accuracy of 0.94, precision of 0.97, and recall of 0.95. Importantly, our approach offers accurate predictions in cases that pathologists cannot resolve and that require additional ISH testing. We confirmed our findings in an independent dataset collected in a different clinical centre. The attention-based CNN exploits morphological information in microscopy images and is superior to a predictive model based on the staining intensity only. We demonstrate that our approach not only automates an important diagnostic process for GEA patients but also paves the way for the discovery of new morphological features that were previously unknown for GEA pathology.

Sections du résumé

BACKGROUND
Fast and accurate diagnostics are key for personalised medicine. Particularly in cancer, precise diagnosis is a prerequisite for targeted therapies, which can prolong lives. In this work, we focus on the automatic identification of gastroesophageal adenocarcinoma (GEA) patients that qualify for a personalised therapy targeting epidermal growth factor receptor 2 (HER2). We present a deep-learning method for scoring microscopy images of GEA for the presence of HER2 overexpression.
METHODS
Our method is based on convolutional neural networks (CNNs) trained on a rich dataset of 1602 patient samples and tested on an independent set of 307 patient samples. We additionally verified the CNN's generalisation capabilities with an independent dataset with 653 samples from a separate clinical centre. We incorporated an attention mechanism in the network architecture to identify the tissue regions, which are important for the prediction outcome. Our solution allows for direct automated detection of HER2 in immunohistochemistry-stained tissue slides without the need for manual assessment and additional costly in situ hybridisation (ISH) tests.
RESULTS
We show accuracy of 0.94, precision of 0.97, and recall of 0.95. Importantly, our approach offers accurate predictions in cases that pathologists cannot resolve and that require additional ISH testing. We confirmed our findings in an independent dataset collected in a different clinical centre. The attention-based CNN exploits morphological information in microscopy images and is superior to a predictive model based on the staining intensity only.
CONCLUSIONS
We demonstrate that our approach not only automates an important diagnostic process for GEA patients but also paves the way for the discovery of new morphological features that were previously unknown for GEA pathology.

Identifiants

pubmed: 36717673
doi: 10.1038/s41416-023-02143-y
pii: 10.1038/s41416-023-02143-y
pmc: PMC10050393
doi:

Substances chimiques

ErbB Receptors EC 2.7.10.1

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1369-1376

Informations de copyright

© 2023. The Author(s).

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Auteurs

Juan I Pisula (JI)

Data science of Bioimages Lab, Faculty of Medicine and University Hospital Cologne, Center for Molecular Medicine Cologne (CMMC), University of Cologne, 50931, Cologne, Germany.

Rabi R Datta (RR)

Department of General, Visceral, Cancer and Transplantation Surgery, University of Cologne, 50937, Cologne, Germany.

Leandra Börner Valdez (LB)

Department of General, Visceral, Cancer and Transplantation Surgery, University of Cologne, 50937, Cologne, Germany.

Jan-Robert Avemarg (JR)

Faculty of Mathematics and Computer Science, Friedrich Schiller University Jena, 07743, Jena, Germany.

Jin-On Jung (JO)

Department of General, Visceral, Cancer and Transplantation Surgery, University of Cologne, 50937, Cologne, Germany.

Patrick Plum (P)

Department of General, Visceral, Cancer and Transplantation Surgery, University of Cologne, 50937, Cologne, Germany.

Heike Löser (H)

Institute of Pathology, University of Cologne, 50937, Cologne, Germany.

Philipp Lohneis (P)

Institute of Pathology, University of Cologne, 50937, Cologne, Germany.

Monique Meuschke (M)

Faculty of Mathematics and Computer Science, Friedrich Schiller University Jena, 07743, Jena, Germany.

Daniel Pinto Dos Santos (DP)

Department of Radiology, University of Cologne, 50937, Cologne, Germany.

Florian Gebauer (F)

Department of General, Visceral, Cancer and Transplantation Surgery, University of Cologne, 50937, Cologne, Germany.

Alexander Quaas (A)

Institute of Pathology, University of Cologne, 50937, Cologne, Germany.

Axel Walch (A)

Research Unit Analytical Pathology, Helmholtz Zentrum München, 85764, Neuherberg, Germany.

Christiane J Bruns (CJ)

Department of General, Visceral, Cancer and Transplantation Surgery, University of Cologne, 50937, Cologne, Germany.

Kai Lawonn (K)

Faculty of Mathematics and Computer Science, Friedrich Schiller University Jena, 07743, Jena, Germany.

Felix C Popp (FC)

Department of General, Visceral, Cancer and Transplantation Surgery, University of Cologne, 50937, Cologne, Germany.

Katarzyna Bozek (K)

Data science of Bioimages Lab, Faculty of Medicine and University Hospital Cologne, Center for Molecular Medicine Cologne (CMMC), University of Cologne, 50931, Cologne, Germany. k.bozek@uni-koeln.de.
Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany. k.bozek@uni-koeln.de.

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