Academic Unit for Translational Medical Sciences, School of Medicine, University of Nottingham, Nottingham, UK.
Department of Pathology, Faculty of Medicine, Assiut University, Assiut, Egypt.
Br J Cancer. 2023 Nov;129(11):1747-1758. doi: 10.1038/s41416-023-02451-3. Epub 2023 Sep 30.
BACKGROUND: Tumour infiltrating lymphocytes (TILs) are a prognostic parameter in triple-negative and human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC). However, their role in luminal (oestrogen receptor positive and HER2 negative (ER + /HER2-)) BC remains unclear. In this study, we used artificial intelligence (AI) to assess the prognostic significance of TILs in a large well-characterised cohort of luminal BC. METHODS: Supervised deep learning model analysis of Haematoxylin and Eosin (H&E)-stained whole slide images (WSI) was applied to a cohort of 2231 luminal early-stage BC patients with long-term follow-up. Stromal TILs (sTILs) and intratumoural TILs (tTILs) were quantified and their spatial distribution within tumour tissue, as well as the proportion of stroma involved by sTILs were assessed. The association of TILs with clinicopathological parameters and patient outcome was determined. RESULTS: A strong positive linear correlation was observed between sTILs and tTILs. High sTILs and tTILs counts, as well as their proximity to stromal and tumour cells (co-occurrence) were associated with poor clinical outcomes and unfavourable clinicopathological parameters including high tumour grade, lymph node metastasis, large tumour size, and young age. AI-based assessment of the proportion of stroma composed of sTILs (as assessed visually in routine practice) was not predictive of patient outcome. tTILs was an independent predictor of worse patient outcome in multivariate Cox Regression analysis. CONCLUSION: AI-based detection of TILs counts, and their spatial distribution provides prognostic value in luminal early-stage BC patients. The utilisation of AI algorithms could provide a comprehensive assessment of TILs as a morphological variable in WSIs beyond eyeballing assessment.
背景:肿瘤浸润淋巴细胞(TILs)是三阴性和人表皮生长因子受体 2(HER2)阳性乳腺癌(BC)的预后参数。然而,它们在管腔(雌激素受体阳性和 HER2 阴性(ER+/HER2-))BC 中的作用仍不清楚。在这项研究中,我们使用人工智能(AI)来评估 TILs 在大型特征明确的管腔 BC 队列中的预后意义。
方法:对 2231 例具有长期随访的管腔早期 BC 患者的苏木精和伊红(H&E)染色全切片图像(WSI)进行有监督的深度学习模型分析。量化了基质 TILs(sTILs)和肿瘤内 TILs(tTILs),并评估了它们在肿瘤组织内的空间分布以及 sTILs 所涉及的基质比例。确定了 TILs 与临床病理参数和患者结局的关系。
结果:观察到 sTILs 和 tTILs 之间存在很强的正线性相关性。高 sTILs 和 tTILs 计数,以及它们与基质和肿瘤细胞的接近程度(共发生)与不良的临床结局和不利的临床病理参数相关,包括高肿瘤分级、淋巴结转移、大肿瘤大小和年轻年龄。基于 AI 的评估(在常规实践中通过肉眼评估)sTILs 组成的基质比例与患者结局无预测价值。在多变量 Cox 回归分析中,tTILs 是患者预后不良的独立预测因子。
结论:基于 AI 的 TILs 计数及其空间分布的检测为管腔早期 BC 患者提供了预后价值。AI 算法的应用可以提供对 TILs 作为 WSI 中形态学变量的全面评估,超越肉眼评估。
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