Department of Hematology, Shengjing Hospital, China Medical University, Shenyang, 110000, China; Division of Hematology, Mayo Clinic, Rochester, MN, 55905, USA.
Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, 55905, USA.
Hum Pathol. 2018 Aug;78:97-105. doi: 10.1016/j.humpath.2018.04.009. Epub 2018 Apr 23.
Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver malignant tumor and has a poor prognosis. The prognostic factors associated with outcome remain poorly defined. In this study, we investigated the role of an important cell apoptosis initiator, Bcl-2 interacting mediator of cell death (Bim), by evaluating its expression and association with other clinicopathological features in ICCs. We analyzed 56 cases of ICC with clinical follow-up. The expression of Bim in ICC cells and other cellular components was evaluated by immunohistochemistry. Bim expression was considered up-regulated if Bim was detected in 10% or more of tumor cells. Of the 56 ICC samples, 19 (34%) had high Bim expression level, 15 (27%) were completely negative, and 22 (39%) were classified as low Bim expression (<10% positivity). Patients who had tumors with high Bim level had significantly longer overall survival than did those with low or no staining (median survival, 7.6 versus 2.6 years; hazard ratio, 0.40; P = .006). High Bim expression was also correlated with low Ki-67 index, and more importantly, none of the tumors with high Bim expression had lymph node metastases at the time of surgery. Our study demonstrates that Bim is an important and independent prognostic factor in ICC. Tumors with high Bim expression are associated with better prognosis through inhibiting tumor cell proliferation and metastatic ability. The development of new agents directly or indirectly targeting Bim may provide promising anticancer treatments.
肝内胆管细胞癌（ICC）是第二常见的原发性肝脏恶性肿瘤，预后较差。与预后相关的预后因素仍未明确。在这项研究中，我们通过评估其在 ICC 中的表达及其与其他临床病理特征的关系，研究了重要的细胞凋亡起始因子 Bcl-2 相互作用的细胞死亡介质（Bim）的作用。我们分析了 56 例具有临床随访的 ICC 病例。通过免疫组织化学评估 ICC 细胞和其他细胞成分中 Bim 的表达。如果在 10％或更多的肿瘤细胞中检测到 Bim，则认为 Bim 表达上调。在 56 个 ICC 样本中，19 个（34％）具有高 Bim 表达水平，15 个（27％）完全为阴性，22 个（39％）被归类为低 Bim 表达（<10％阳性）。具有高 Bim 水平肿瘤的患者的总生存时间明显长于低或无染色的患者（中位生存时间，7.6 与 2.6 年；风险比，0.40；P =.006）。高 Bim 表达还与低 Ki-67 指数相关，更重要的是，在手术时具有高 Bim 表达的肿瘤均无淋巴结转移。我们的研究表明，Bim 是 ICC 的重要独立预后因素。高 Bim 表达的肿瘤通过抑制肿瘤细胞增殖和转移能力与更好的预后相关。直接或间接靶向 Bim 的新药物的开发可能提供有前途的抗癌治疗方法。
