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EGFR Mutation Detection in Whole Slide Images of Non-Small Cell Lung Cancers Using a Two-Stage Deep Transfer Learning

Michele Zanoletti1, Filippo Ugolini2, Laila El Bachiri3

  • 1Institute of Clinical Physiology, National Research Council, Pisa, Italy.

Cancer Medicine
|September 18, 2025
PubMed
Summary

This study utilized artificial intelligence (AI) to analyze lung cancer (LC) tissue images, accurately distinguishing cancerous from healthy cells. While AI shows promise for LC diagnosis, directly detecting EGFR mutations from standard slides remains challenging.

Keywords:
CNNEGFR mutationWSIadenocarcinomaartificial intelligencedeep learningdigital pathologyexplainabilitynon‐small cell lung cancer

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Area of Science:

  • Oncology
  • Computational Pathology
  • Artificial Intelligence in Medicine

Background:

  • Lung cancer (LC) is a leading cause of cancer mortality globally, with non-small cell lung cancer being the most prevalent subtype.
  • Current LC treatment relies on molecular profiling, particularly detecting Epidermal Growth Factor Receptor (EGFR) gene mutations, which are critical for targeted tyrosine kinase inhibitor therapy.

Purpose of the Study:

  • To evaluate the efficacy of Convolutional Neural Networks (CNNs) in distinguishing healthy lung tissue from cancerous tissue.
  • To assess the potential of CNNs in identifying EGFR-mutated tumor tissue from standard histopathological slides.
  • To utilize Explainable AI (Grad-CAM) for visualizing the decision-making process of the CNN models.

Main Methods:

  • Two InceptionResNet-V2 based CNNs were applied to Whole Slide Images (WSIs) of lung cancer tissue.
  • An Explainable AI technique, Grad-CAM, was integrated to provide visual insights into model predictions.
  • The study analyzed 259 lung cancer cases from three distinct Italian centers.

Main Results:

  • The CNNs achieved high accuracy (96.17%) in differentiating healthy from cancerous tissue, with an AUC of 0.99.
  • For EGFR mutation detection within cancer tissue, the models reached an accuracy of 76.67% and an AUC of 0.77.
  • Explainable AI provided visual insights into the model's classification process.

Conclusions:

  • The tested CNNs demonstrate significant potential in aiding lung cancer diagnosis, particularly in differentiating tumor from healthy tissue.
  • Directly predicting EGFR mutational status from routine H&E slides using these AI models presents challenges.
  • The findings suggest that valuable predictive information for LC diagnosis can be extracted from standard histopathological slides via AI analysis.