Department of Pathology and Laboratory Medicine, Donald and Barbara Zucker School of Medicine at Northwell, United States.
Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, United States.
Pathol Res Pract. 2021 Apr;220:153378. doi: 10.1016/j.prp.2021.153378. Epub 2021 Feb 13.
Cancer comprises epithelial tumor cells and associated stroma, often times referred to as the "tumoral microenvironment". Cancer-associated fibroblasts (CAFs) are the most notable components of the tumor mesenchyme. CAFs promote the initiation of cancer through angiogenesis, invasion and metastasis. Histologically, the differentiation of stroma has been reported to correlate with prognostic outcomes in patients with colorectal cancer. This review summarizes our current understanding of the extracellular matrix (ECM) in colorectal carcinoma (CRC), showcasing the functions of CAFs and its role in stromal differentiation (SD). We also review current state-of-the-art biology, histopathology, computation, and genomics in the setting of the stroma. SD is distinctive morphologically, and is easily recognized by a surgical pathologist; we offer a lexicon and guide for discovering the essence of stroma, as well as an incipient vision of the future for computation and molecular genomics. We propose that the mesenchymal phenotype, which encompasses a cancer migratory/metastatic capacity, could occur through the process of SD. Looking forward, pathologists will need to invest time and energy into SD, embracing the concept and propagating its use. For patients with colorectal cancer, stroma is a brave new frontier, one not only rich in biologic diversity, but also potentially critical for therapeutic decision making.
癌症包括上皮肿瘤细胞和相关的基质，通常被称为“肿瘤微环境”。癌症相关成纤维细胞（CAFs）是肿瘤间质中最显著的成分。CAFs 通过血管生成、侵袭和转移促进癌症的发生。组织学上，已经报道了基质的分化与结直肠癌患者的预后结果相关。本综述总结了我们目前对结直肠癌（CRC）中细胞外基质（ECM）的理解，展示了 CAFs 的功能及其在基质分化（SD）中的作用。我们还回顾了目前在基质背景下的生物学、组织病理学、计算和基因组学的最新进展。SD 在形态上具有独特性，容易被外科病理学家识别；我们提供了一个发现基质本质的词汇和指南，以及对计算和分子基因组学未来的初步展望。我们提出，包含癌症迁移/转移能力的间质表型可能通过 SD 过程发生。展望未来，病理学家将需要投入时间和精力来研究 SD，接受这一概念并推广其应用。对于结直肠癌患者来说，基质是一个崭新的前沿领域，不仅具有丰富的生物学多样性，而且对治疗决策也可能至关重要。
