Cited by 193AI in cancer detectionRadiomics and Machine Learning in Medical ImagingCancer Immunotherapy and Biomarkers

Deep learning-based image analysis predicts PD-L1 status from H&E-stained histopathology images in breast cancer

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Shamai, Gil, Livne, Amir, Polónia, António, Sabo, Edmond, Cretu, Alexandra, Bar-Sela, Gil, Kimmel, Ron·2022·Nature Communications

Abstract

Programmed death ligand-1 (PD-L1) has been recently adopted for breast cancer as a predictive biomarker for immunotherapies. The cost, time, and variability of PD-L1 quantification by immunohistochemistry (IHC) are a challenge. In contrast, hematoxylin and eosin (H&E) is a robust staining used routinely for cancer diagnosis. Here, we show that PD-L1 expression can be predicted from H&E-stained images by employing state-of-the-art deep learning techniques. With the help of two expert pathologists and a designed annotation software, we construct a dataset to assess the feasibility of PD-L1 prediction from H&E in breast cancer. In a cohort of 3,376 patients, our system predicts the PD-L1 status in a high area under the curve (AUC) of 0.91 - 0.93. Our system is validated on two external datasets, including an independent clinical trial cohort, showing consistent prediction performance. Furthermore, the proposed system predicts which cases are prone to pathologists miss-interpretation, showing it can serve as a decision support and quality assurance system in clinical practice.

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  • Other efforts have used AI on H&E images to predict TIL presence and PD-L1 expression status in breast cancer.

    “Other efforts have used AI on H&E images to directly predict TIL presence (85,86), a notable prognostic and predictive biomarker in breast cancer, and programmed cell death ligand 1 (PD-L1) expression status, a predictive biomarker for immunotherapies (87).”

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Research works printed but not linked: 5

  1. [3]Humphries MP A J. Oncol. 2018 2018 2937012 30651729 PMC6311859
  2. [37]Gulum MA Trombley CM Kantardzic M A review of explainable deep learning cancer detection models in medical imaging NATO Adv. Sci. Inst. Ser. E Appl. Sci. 2021 11 4573
  3. [39]Selvaraju, R. R., Cogswell, M. & Das, A. Grad-cam: Visual explanations from deep networks via gradient-based localization. Proc. Estonian Acad. Sci. Biol. Ecol. https://arxiv.org/abs/1610.02391. · arXiv
  4. [41]Roche, V. Ventana PD-L1 (SP142) Assay interpretation guide for triple-negative breast carcinoma (TNBC). https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=Ventana+PD-L1+%28SP142%29+Assay+interpretation+guide+for+triple-negative+breast+carcinoma+%28TNBC%29&btnG= (2019).
  5. [44]Liu et al. On the variance of the adaptive learning rate and beyond. Preprint at arXiv:1908. 03265.

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Authors
Shamai, G., Livne, A., Polónia, A., Sabo, E., Cretu, A., Bar-Sela, G., & Kimmel, R.
Affiliations
  • Technion – Israel Institute of Technology (IL)
  • Universidade do Porto (PT)
  • Carmel Medical Center (IL)
Corresponding author
Shamai, Gil
Venue
Nature Communications
Published
2022-11-08
Volume
13
Issue
1
Pages
6753-6753
ISSN
2041-1723 (ISSN-L)
OpenAlex
W4308573933
Cited by
193
References
40
Citations by year
2026: 38 · 2025: 80 · 2024: 55 · 2023: 19 · 2022: 1
FWCI
12.70
Type
journal article
Language
en
Open access
Locations
  • Nature Communications (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
Israel Science Foundation (3864/21, 679/18)
Topics
  • Physical Sciences › Computer Science › Artificial Intelligence › AI in cancer detection
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Radiomics and Machine Learning in Medical Imaging
  • Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
Keywords
breast cancer, deep learning, immunotherapy predictive biomarker, immunohistochemistry alternative, annotation tools, decision support system, quality assurance in pathology
MeSH terms
Deep Learning, Breast Neoplasms, Female, Hematoxylin, Humans, Lung Neoplasms, Staining and Labeling, Biomarkers, Tumor, B7-H1 Antigen

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