近日，美国加州斯坦福大学医学院Michael Angelo和Robert B. West共同合作取得了重要进展，他们发现了向浸润性乳腺癌的转变与肿瘤间质的结构和组成的渐进性变化有关。这一研究成果于2022年1月20日在线发表于《细胞》杂志上。
为了了解伴随着向浸润性乳腺癌过渡的肿瘤微环境的变化，研究人员使用了飞行时间的多重离子束成像（MIBI-TOF）和37种抗体染色，利用机器学习工具进行细胞分割、基于像素的聚类和物体形态测量的方法，对79个临床注释的手术切除样本进行了分析。正常乳腺与患者匹配的DCIS和IBC的比较显示了四种TME状态之间的协调转换，这些状态是根据肌上皮细胞、成纤维细胞和免疫细胞的位置和功能来划分的。
令人惊讶的是，在未发生 IBC 的 DCIS 患者中，肌上皮破坏更为严重，这表明该过程可能对复发具有保护作用。综上所述，这项HTAN乳腺癌前期图谱研究为IBC复发的驱动因素提供了见解，并强调了TME在调节这些过程中的重要性。
据悉，原位导管癌是一种侵润性前病变，被认为是侵润性乳腺癌的前兆。
附：英文原文
Title: Transition to invasive breast cancer is associated with progressive changes in the structure and composition of tumor stroma
Author: Tyler Risom, David R. Glass, Inna Averbukh, Candace C. Liu, Alex Baranski, Adam Kagel, Erin F. McCaffrey, Noah F. Greenwald, Belén Rivero-Gutiérrez, Siri H. Strand, Sushama Varma, Alex Kong, Leeat Keren, Sucheta Srivastava, Chunfang Zhu, Zumana Khair, Deborah J. Veis, Katherine Deschryver, Sujay Vennam, Carlo Maley, E. Shelley Hwang, Jeffrey R. Marks, Sean C. Bendall, Graham A. Colditz, Robert B. West, Michael Angelo
Issue&Volume: 2022/01/20
Abstract: Ductal carcinoma in situ (DCIS) is a pre-invasive lesion that is thought to be a precursor to invasive breast cancer (IBC). To understand the changes in the tumor microenvironment (TME) accompanying transition to IBC, we used multiplexed ion beam imaging by time of flight (MIBI-TOF) and a 37-plex antibody staining panel to interrogate 79 clinically annotated surgical resections using machine learning tools for cell segmentation, pixel-based clustering, and object morphometrics. Comparison of normal breast with patient-matched DCIS and IBC revealed coordinated transitions between four TME states that were delineated based on the location and function of myoepithelium, fibroblasts, and immune cells. Surprisingly, myoepithelial disruption was more advanced in DCIS patients that did not develop IBC, suggesting this process could be protective against recurrence. Taken together, this HTAN Breast PreCancer Atlas study offers insight into drivers of IBC relapse and emphasizes the importance of the TME in regulating these processes.
DOI: 10.1016/j.cell.2021.12.023
Source: https://www.cell.com/cell/fulltext/S0092-8674(21)01486-0