Laboratory for Translational Breast Cancer Research, Department of Oncology, KU Leuven, Herestraat 49, box 810, Leuven, 3000, Belgium.
Department of Pathology, University Hospitals Leuven, Leuven, Belgium.
Clin Exp Metastasis. 2024 Oct;41(5):699-705. doi: 10.1007/s10585-024-10279-1. Epub 2024 Mar 29.
Metastatic breast cancer (mBC) remains incurable and liver metastases (LM) are observed in approximately 50% of all patients with mBC. In some cases, surgical resection of breast cancer liver metastases (BCLM) is associated with prolonged survival. However, there are currently no validated marker to identify these patients. The interactions between the metastatic cancer cells and the liver microenvironment result in two main histopathological growth patterns (HGP): replacement (r-HGP), characterized by a direct contact between the cancer cells and the hepatocytes, and desmoplastic (d-HGP), in which a fibrous rim surrounds the tumor cells. In patients who underwent resection of BCLM, the r-HGP is associated with a worse postoperative prognosis than the d-HGP. Here, we aim at unraveling the biological differences between these HGP within ten patients presenting both HGP within the same metastasis. The transcriptomic analyses reveal overexpression of genes involved in cell cycle, DNA repair, vessel co-option and cell motility in r-HGP while angiogenesis, wound healing, and several immune processes were found overexpressed in d-HGP LM. Understanding the biology of the LM could open avenues to refine treatment of BC patients with LM.
转移性乳腺癌（MBC）仍然无法治愈，约 50%的 MBC 患者会发生肝转移。在某些情况下，乳腺癌肝转移的手术切除（BCLM）与延长生存相关。然而，目前还没有经过验证的标志物来识别这些患者。转移性癌细胞与肝微环境的相互作用导致两种主要的组织病理学生长模式（HGP）：替代型（r-HGP），其特征是癌细胞与肝细胞直接接触，纤维型（d-HGP），其中肿瘤细胞被纤维边缘环绕。在接受 BCLM 切除的患者中，r-HGP 与术后预后较差相关，而 d-HGP 则预后较好。在这里，我们旨在阐明十个同时具有两种 HGP 的患者中同一转移灶内这两种 HGP 之间的生物学差异。转录组分析显示，r-HGP 中与细胞周期、DNA 修复、血管选择和细胞运动相关的基因表达过度，而 d-HGP 中血管生成、伤口愈合和几种免疫过程过度表达。了解 LM 的生物学特性可能为改善 LM 乳腺癌患者的治疗提供途径。
