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Updated: Jul 12, 2026
Multiplex Immunohistochemical Analysis of the Spatial Immune Cell Landscape of the Tumor Microenvironment
Published on: August 18, 2023
Deep learning based automated HER2 score prediction using immunohistochemistry histopathological images: a
Juan Ma1, Lijun Song1, Mireguli Damaola2
1Medical Imaging Center, Xinjiang Medical University Affiliated Fourth Hospital, Urumqi, China.
Background:
HER2 is a critical prognostic biomarker in breast cancer and associated with aggressive tumor biology. Current IHC scoring is subjective and labor-intensive. Deep learning has demonstrated success in histopathological image analysis, yet HER2 IHC automation remains underexplored. External-center validation is essential to establish clinical credibility and demonstrate robustness across diverse institutional practices and imaging protocols.
Methods:
This dual-center retrospective study analyzed 135 HER2 IHC whole-slide images from 118 breast cancer patients labeled as 1+, 2+, or 3+ by standard clinical criteria. Two board-certified pathologists manually annotated tumor-enriched ROIs, which were tiled into non-overlapping 512x512 patches; tiles with >60% white background were excluded. Patches were harmonized using a modified Macenko color normalization and augmented during training. Six pretrained deep learning models (AlexNet, VGG16, ResNet34, DenseNet121, Inception, Swin Transformer) were trained with patient-level splits and evaluated on an independent test set using macro-averaged AUC and complementary metrics.
Results:
The cohort included 118 patients with comparable age and largely similar baseline imaging/pathologic characteristics across groups, although clinical symptoms and lymph node status differed. On the independent test set, all models showed good discrimination for three-class HER2 grading, with AlexNet performing best (macro-AUC 0.971), followed by VGG16 (0.967). For AlexNet, per-class AUCs were 0.980 (1+), 0.955 (2+), and 0.979 (3+); most errors occurred between adjacent grades (1+/2+, 2+/3+). Grad-CAM highlighted strongly stained tumor regions driving predictions.
Conclusion:
A deep learning framework showed encouraging patch-level performance for three-class HER2 IHC score prediction in a pooled dual-center retrospective cohort. This approach may assist pathologists by improving scoring consistency and identifying borderline or low-confidence cases that require careful review and, when clinically indicated, confirmatory testing.