The Beijer Laboratory, Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden.
Department of Information Technology, Uppsala University, Uppsala, Sweden.
J Pathol. 2022 Sep;258(1):4-11. doi: 10.1002/path.5981. Epub 2022 Jul 12.
Vascular remodeling is common in human cancer and has potential as future biomarkers for prediction of disease progression and tumor immunity status. It can also affect metastatic sites, including the tumor-draining lymph nodes (TDLNs). Dilation of the high endothelial venules (HEVs) within TDLNs has been observed in several types of cancer. We recently demonstrated that it is a premetastatic effect that can be linked to tumor invasiveness in breast cancer. Manual visual assessment of changes in vascular morphology is a tedious and difficult task, limiting high-throughput analysis. Here we present a fully automated approach for detection and classification of HEV dilation. By using 12,524 manually classified HEVs, we trained a deep-learning model and created a graphical user interface for visualization of the results. The tool, named the HEV-finder, selectively analyses HEV dilation in specific regions of the lymph nodes. We evaluated the HEV-finder's ability to detect and classify HEV dilation in different types of breast cancer compared to manual annotations. Our results constitute a successful example of large-scale, fully automated, and user-independent, image-based quantitative assessment of vascular remodeling in human pathology and lay the ground for future exploration of HEV dilation in TDLNs as a biomarker. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
血管重构在人类癌症中很常见,具有作为预测疾病进展和肿瘤免疫状态的未来生物标志物的潜力。它还可以影响转移部位,包括肿瘤引流淋巴结 (TDLNs)。已经在几种类型的癌症中观察到 TDLNs 内高内皮静脉 (HEV) 的扩张。我们最近证明,这是一种可以与乳腺癌侵袭性相关的前转移效应。手动评估血管形态变化是一项繁琐且困难的任务,限制了高通量分析。在这里,我们提出了一种用于检测和分类 HEV 扩张的全自动方法。通过使用 12524 个手动分类的 HEV,我们训练了一个深度学习模型,并创建了一个图形用户界面来可视化结果。该工具名为 HEV-finder,可选择性地分析淋巴结特定区域的 HEV 扩张。我们评估了 HEV-finder 与手动注释相比,在不同类型的乳腺癌中检测和分类 HEV 扩张的能力。我们的结果构成了大规模、全自动和用户独立的基于图像的人类病理学中血管重构定量评估的成功范例,并为未来探索 TDLNs 中 HEV 扩张作为生物标志物奠定了基础。