Zhang Xiao-Fang, Dong Min, Pan Yu-Hang, Chen Jian-Ning, Huang Xiang-Qi, Jin Yi, Shao Chun-Kui
Department of Pathology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510630, China; Guangdong Provincial Key Laboratory of Liver Disease Research, Guangzhou, China.
Guangdong Provincial Key Laboratory of Liver Disease Research, Guangzhou, China; Department of Medical Oncology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510630, China.
Hum Pathol. 2017 Jul;65:92-100. doi: 10.1016/j.humpath.2017.04.014. Epub 2017 Apr 27.
Intrahepatic cholangiocarcinoma (ICC) is a highly malignant neoplasm and lack of effective treatment, characterized by dense desmoplastic stroma rich in cancer-associated fibroblasts (CAFs), which have been indicated to facilitate tumor progression in several types of human cancer. However, the clinical relevance of CAFs in ICC has not been fully characterized. Here, we evaluated the histological phenotype of CAFs and immunohistochemical expressions of α-SMA, FSP-1, and PDGFRβ in 71 ICC cases, and found that immature CAF phenotype was significantly associated with lymph node metastasis (P=.045), advanced TNM stage (P=.025) and poor 5-year overall survival (OS) (38.5% versus 78.6%, P=.015). In addition, α-SMA, FSP-1, and PDGFRβ were positively expressed in stromal fibroblasts in 63.4% (45/71), 84.5% (60/71), and 78.9% (56/71) of patients, respectively. Positive expression of α-SMA was correlated with poor differentiation (P=.032); FSP-1 expression in stromal fibroblasts was linked with lymph node metastasis (P=.022) and immature phenotype (P=.048). What's more, positive expression of FSP-1 in cancer cells was observed in 22.5% (16/71) of cases and was correlated with worse 5-year OS (36.4% versus 76.7%, P=.014). Importantly, in multivariate analysis, histological CAF phenotype was an independent prognostic factor for OS in ICC. Our findings demonstrated histological categorization of CAFs was a useful predictor for prognosis, providing new evidence that CAFs play a crucial role in tumor progression and can serve as potential therapeutic targets in ICC.
肝内胆管癌（ICC）是一种高度恶性肿瘤，且缺乏有效的治疗方法，其特征是存在富含癌症相关成纤维细胞（CAF）的致密促纤维增生性基质，在几种人类癌症类型中，这些细胞已被证明可促进肿瘤进展。然而，CAF在ICC中的临床相关性尚未完全明确。在此，我们评估了71例ICC病例中CAF的组织学表型以及α-SMA、FSP-1和PDGFRβ的免疫组化表达，发现不成熟的CAF表型与淋巴结转移显著相关（P = 0.045）、TNM分期较晚（P = 0.025）以及5年总生存率较差（38.5%对78.6%，P = 0.015）。此外，α-SMA、FSP-1和PDGFRβ在63.4%（45/71）、84.5%（60/71）和78.9%（56/71）的患者的基质成纤维细胞中呈阳性表达。α-SMA的阳性表达与低分化相关（P = 0.032）；基质成纤维细胞中FSP-1的表达与淋巴结转移（P = 0.022）和不成熟表型（P = 0.048）有关。此外，在22.5%（16/71）的病例中观察到癌细胞中FSP-1呈阳性表达，且与较差的5年总生存率相关（36.4%对76.7%，P = 0.014）。重要的是，在多变量分析中，组织学CAF表型是ICC患者总生存率的独立预后因素。我们的研究结果表明，CAF的组织学分类是预后的有用预测指标，提供了新的证据表明CAF在肿瘤进展中起关键作用，并可作为ICC潜在的治疗靶点。
