Leduc Sophia, De Schepper Maxim, Richard François, Maetens Marion, Pabba Anirudh, Borremans Kristien, Jaekers Joris, Latacz Emily, Zels Gitte, Bohlok Ali, Van Baelen Karen, Nguyen Ha Linh, Geukens Tatjana, Dirix Luc, Larsimont Denis, Vankerckhove Sophie, Santos Eva, Oliveira Rui Caetano, Dede Kristòf, Kulka Janina, Borbala Székely, Salamon Ferenc, Madaras Lilla, Marcell Szasz A, Lucidi Valerio, Meyer Yannick, Topal Baki, Verhoef Cornelis, Engstrand Jennie, Moro Carlos Fernandez, Gerling Marco, Bachir Imane, Biganzoli Elia, Donckier Vincent, Floris Giuseppe, Vermeulen Peter, Desmedt Christine
Laboratory for Translational Breast Cancer Research, Department of Oncology, KU Leuven, Leuven, Belgium.
Department of Pathology, University Hospitals Leuven, Leuven, Belgium.
NPJ Breast Cancer. 2023 Dec 15;9(1):100. doi: 10.1038/s41523-023-00602-6.
Liver is the third most common organ for breast cancer (BC) metastasis. Two main histopathological growth patterns (HGP) exist in liver metastases (LM): desmoplastic and replacement. Although a reduced immunotherapy efficacy is reported in patients with LM, tumor-infiltrating lymphocytes (TIL) have not yet been investigated in BCLM. Here, we evaluate the distribution of the HGP and TIL in BCLM, and their association with clinicopathological variables and survival. We collect samples from surgically resected BCLM (n = 133 patients, 568 H&E sections) and post-mortem derived BCLM (n = 23 patients, 97 H&E sections). HGP is assessed as the proportion of tumor liver interface and categorized as pure-replacement ('pure r-HGP') or any-desmoplastic ('any d-HGP'). We score the TIL according to LM-specific guidelines. Associations with progression-free (PFS) and overall survival (OS) are assessed using Cox regressions. We observe a higher prevalence of 'any d-HGP' (56%) in the surgical samples and a higher prevalence of 'pure r-HGP' (83%) in the post-mortem samples. In the surgical cohort, no evidence of the association between HGP and clinicopathological characteristics is observed except with the laterality of the primary tumor (p value = 0.049) and the systemic preoperative treatment before liver surgery (p value = .039). TIL is less prevalent in 'pure r-HGP' as compared to 'any d-HGP' (p value = 0.001). 'Pure r-HGP' predicts worse PFS (HR: 2.65; CI: (1.45-4.82); p value = 0.001) and OS (HR: 3.10; CI: (1.29-7.46); p value = 0.011) in the multivariable analyses. To conclude, we demonstrate that BCLM with a 'pure r-HGP' is associated with less TIL and with the worse outcome when compared with BCLM with 'any d-HGP'. These findings suggest that HGP could be considered to refine treatment approaches.
肝脏是乳腺癌（BC）转移的第三大常见器官。肝转移（LM）存在两种主要的组织病理学生长模式（HGP）：促结缔组织增生型和替代型。尽管有报道称LM患者的免疫治疗疗效降低，但尚未对乳腺导管原位癌肝转移（BCLM）中的肿瘤浸润淋巴细胞（TIL）进行研究。在此，我们评估BCLM中HGP和TIL的分布，以及它们与临床病理变量和生存率的关联。我们收集了手术切除的BCLM样本（n = 133例患者，568张苏木精-伊红染色切片）和尸检获得的BCLM样本（n = 23例患者，97张苏木精-伊红染色切片）。HGP被评估为肿瘤与肝脏界面的比例，并分为纯替代型（“纯r-HGP”）或任何促结缔组织增生型（“任何d-HGP”）。我们根据LM特异性指南对TIL进行评分。使用Cox回归评估与无进展生存期（PFS）和总生存期（OS）的关联。我们观察到手术样本中“任何d-HGP”的患病率较高（56%），而尸检样本中“纯r-HGP”的患病率较高（83%）。在手术队列中，除了与原发肿瘤的侧别（p值 = 0.049）和肝手术前的全身术前治疗（p值 = 0.039）外，未观察到HGP与临床病理特征之间存在关联的证据。与“任何d-HGP”相比，“纯r-HGP”中TIL的患病率较低（p值 = 0.001）。在多变量分析中，“纯r-HGP”预测PFS较差（HR：2.65；CI：（1.45 - 4.82）；p值 = 0.001）和OS较差（HR：3.10；CI：（1.29 - 7.46）；p值 = 0.011）。总之，我们证明与具有“任何d-HGP” 的BCLM相比，具有“纯r-HGP” 的BCLM与较少的TIL相关，且预后较差。这些发现表明，HGP可被视为优化治疗方法的依据。
