Ge Chong, Shi Yi, Wang Wei, Zhang Anli, Huang Mengqi, Zhao Fang, Li Ao, Feng Zhenzhong, Wang Minghui, Wu Haibo
Department of Pathology, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230036, China.
Intelligent Pathology Institute, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230036, China.
Diagn Pathol. 2025 Sep 26;20(1):106. doi: 10.1186/s13000-025-01707-1.
Accurate assessment of programmed death-ligand 1 (PD-L1) immunohistochemical (IHC) expression is critical for immunotherapy in patients with non-small cell lung cancer (NSCLC). Yet, interpreting its staining is challenging, time-consuming, and causes inter-observer variability, potentially mis-stratifying patients. This necessitates the development of an artificial intelligence (AI) model to effectively quantify PD-L1 expression. Hence, we developed an AI-based deep-learning approach to automatically assess PD-L1 expression in NSCLC using IHC 22C3 assay-stained whole slide images (WSIs).
A total of 706 patients with NSCLC were included in this study and 1212 WSIs were collected from three distinct study cohorts. We accurately matched the hematoxylin and eosin-stained images of the internal dataset with the IHC WSIs. Foreground regions containing tumor tissue were extracted from WSIs, and a multi-granular multiple-instance learning approach employing instance embeddings with coarse and fine granularities was implemented to extract patch-level morphological features. A multi-grained expression interpreter-based model aggregated these features to stratify PD-L1 expression status.
The model showed strong interpretive ability in all three cohorts and wide applicability to different specimen types. The macro-average area under the receiver operating characteristic curve (AUC) were 0.940/0.915/0.944 for surgical specimens, 0.955/0.844/0.865 for biopsy specimens, and 0.901/0.958/0.883 for metastases.
This study emphasizes the potential benefits of deep learning in automatically, rapidly, and accurately inferring PD-L1 expression from complex IHC images. It also showcases how AI frameworks can improve routine digital pathology workflows in current PD-L1 detection methods.
准确评估程序性死亡配体1(PD-L1)免疫组化(IHC)表达对于非小细胞肺癌(NSCLC)患者的免疫治疗至关重要。然而,解读其染色具有挑战性、耗时且会导致观察者间的差异,可能使患者分层错误。这就需要开发一种人工智能(AI)模型来有效量化PD-L1表达。因此,我们开发了一种基于AI的深度学习方法,使用IHC 22C3检测染色的全切片图像(WSIs)自动评估NSCLC中的PD-L1表达。
本研究共纳入706例NSCLC患者,并从三个不同的研究队列中收集了1212张WSIs。我们将内部数据集的苏木精和伊红染色图像与IHC WSIs精确匹配。从WSIs中提取包含肿瘤组织的前景区域,并采用一种多粒度多实例学习方法,该方法使用具有粗粒度和细粒度的实例嵌入来提取斑块级形态特征。基于多粒度表达解释器的模型汇总这些特征以对PD-L1表达状态进行分层。
该模型在所有三个队列中均显示出强大的解释能力,并且对不同标本类型具有广泛的适用性。手术标本的受试者操作特征曲线(AUC)下的宏平均面积分别为0.940/0.915/0.944,活检标本为0.955/0.844/0.865,转移灶为0.901/0.958/0.883。
本研究强调了深度学习在从复杂的IHC图像中自动、快速且准确地推断PD-L1表达方面的潜在益处。它还展示了AI框架如何在当前的PD-L1检测方法中改善常规数字病理工作流程。