Evidence map›Paper›PMID 41827725›Full record

ArticleCancers2026

3SGAN: Semi-Supervised and Multi-Task GAN for Stain Normalization and Nuclei Segmentation of Histopathological Images.

Yifan Chen, Zhiruo Yang, Guoqing Wu, Qisheng Tang, Kay Ka-Wai Li, Ho-Keung Ng, Zhifeng Shi, Jinhua Yu, Guohui Zhou

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Article in Cancers, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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9 authors.

Yifan ChenCollege of Biomedical Engineering, Fudan University, Shanghai 200438, China.
Zhiruo YangCollege of Biomedical Engineering, Fudan University, Shanghai 200438, China.
Guoqing WuCollege of Biomedical Engineering, Fudan University, Shanghai 200438, China.
Qisheng TangDepartment of Neurosurgery, Huashan Hospital, Fudan University, Shanghai 200040, China.
Kay Ka-Wai LiDepartment of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR, China.ORCID 0000-0001-9588-3042
Ho-Keung NgDepartment of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR, China.ORCID 0000-0002-2614-2213
Zhifeng ShiDepartment of Neurosurgery, Huashan Hospital, Fudan University, Shanghai 200040, China.
Jinhua YuCollege of Biomedical Engineering, Fudan University, Shanghai 200438, China.
Guohui ZhouCollege of Biomedical Engineering, Fudan University, Shanghai 200438, China.ORCID 0000-0001-5135-0631

Funding

National Key R&D Program of China MOST 2023YFC2510000
6 · The paper itself

Abstract

BACKGROUND/

objectivesVariations in staining styles-arising from differences in tissue preparation, scanners, and laboratory protocols-severely compromise the robustness of automated cell segmentation algorithms in digital pathology. Moreover, manual nucleus annotation is extremely labor-intensive, leading to a scarcity of large-scale, fully annotated datasets for supervised nucleus segmentation. This study proposes a novel framework that simultaneously mitigates staining variability and achieves high-accuracy nucleus segmentation using only minimal annotations.

methodsWe present 3SGAN, a multi-task dual-branch generative adversarial network (GAN) that jointly performs stain normalization and nucleus segmentation in a semi-supervised manner. The framework adopts a teacher-student paradigm: a lightweight teacher model (AttCycle) equipped with attention gates generates reliable pseudo-labels, while a high-capacity student model (TransCycle) leveraging a hybrid CNN-Transformer architecture further refines performance. 3SGAN was trained and evaluated on a large dataset of 1408 Whole-Slide Images (WSIs) from two medical institutions, encompassing 101 distinct staining styles, with nucleus-level annotations required for only 5% of the data.

results3SGAN significantly outperformed state-of-the-art methods, achieving superior segmentation accuracy with an F1-score of 0.8140, mean IoU of 0.8201, and AJI of 0.6915. Simultaneously, it demonstrated substantial improvements in stain normalization quality, yielding a low RMSE of 0.0908, high PSNR of 21.0615, and SSIM of 0.8556 on the internal test set. External validation on independent MoNuSeg and PanNuke datasets, as well as on previously untested tumor-rich non-ROI regions from our in-house WSIs, confirmed strong generalizability with excellent stain normalization and top-tier segmentation accuracy across diverse staining protocols, tissue types, and pathological patterns.

conclusionsThe proposed 3SGAN framework demonstrates that high-performance nucleus segmentation and stain normalization can be achieved with minimal annotation requirements, offering a practical and scalable solution for digital pathology applications across diverse clinical settings and staining protocols.

Indexed as

digital pathologygenerative adversarial networksgliomamulti-task learningnuclei segmentationsemi-supervised learningstain normalization

Identifiers

PMID41827725
PMCPMC12984188

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