The Liver Cancer Institute, Zhongshan Hospital and Shanghai Medical School, Fudan University, Key Laboratory for Carcinogenesis and Cancer Invasion, The Chinese Ministry of Education, Shanghai, People's Republic of China.
Department of Breast Surgery, The Obstetrics & Gynecology Hospital of Fudan University, Shanghai, People's Republic of China.
Oncologist. 2018 Dec;23(12):1482-1493. doi: 10.1634/theoncologist.2017-0439. Epub 2018 Sep 26.
Fibrotic tumor stroma (FTS) has been implicated in cancer promotion in several neoplasms. The histological features of FTS are convenient and easily accessible in clinical routine in intrahepatic cholangiocarcinoma (ICC) specimens. The goal of this study was to explore prognostic impacts of the quantity and maturity of FTS on surgical ICC patients. Moreover, we aimed to propose an efficient prognostic nomogram for postoperative ICC patients.
The clinical profiles of 154 consecutive postoperative ICC patients were retrospectively analyzed. Tumor-stroma ratio and morphological maturity of FTS were evaluated on hematoxylin and eosin-stained tumor sections. CD3, CD8, and α-smooth muscle actin (α-SMA) staining were performed on corresponding tissue microarrays. The nomogram was established on variables selected by multivariate analyses and was validated in 10-fold cross-validation.
Rich tumor stroma and strong α-SMA expression were associated with poor overall survival (OS). However, in multivariate analyses, these two biomarkers failed to stratify both OS and recurrence-free survival (RFS). Immature FTS was correlated with tumor multiplicity, advanced clinical stage, and sparser CD3 and CD8 positive tumor-infiltrating lymphocytes (TILs) and was identified as an independent prognostic indicator for both OS and RFS. The nomogram comprising FTS maturity, tumor number, microvascular invasion, and lymph node metastasis possessed higher predictive power relative to conventional staging systems.
Immature FTS was an independent risk factor for survival and was associated with sparser CD3 and CD8 positive TILs in ICC. The prognostic nomogram integrating the maturity of FTS offers a more accurate risk stratification for postoperative ICC patients.
Accumulating evidence has suggested that fibrotic components in tumor microenvironment (TME) play a complicated and vital role in TME reprogramming and cancer progression. However, in clinical practice, the evaluation of fibrotic tumor stroma (FTS) is still neglected to some extent. This study's findings indicated that, in intrahepatic cholangiocarcinoma (ICC), the histological maturity of FTS is a robust prognostic indicator for patients who underwent curative resection. Moreover, prognostic nomogram constructed on the maturity of FTS possessed higher predictive power relative to the conventional tumor-node-metastasis staging systems. Taken together, the evaluation of FTS should be emphasized in clinical routine for more accurate prognostic prediction in postoperative ICC patients.
纤维性肿瘤基质（FTS）已被认为与几种肿瘤的癌症促进有关。FTS 的组织学特征在肝内胆管癌（ICC）标本的临床常规中方便且易于获取。本研究的目的是探讨 FTS 的数量和成熟度对手术 ICC 患者的预后影响。此外，我们旨在为术后 ICC 患者提出一种有效的预后列线图。
回顾性分析 154 例连续接受手术的 ICC 患者的临床资料。在苏木精和伊红染色的肿瘤切片上评估肿瘤基质比和 FTS 的形态成熟度。在相应的组织微阵列上进行 CD3、CD8 和 α-平滑肌肌动蛋白（α-SMA）染色。列线图是基于多变量分析选择的变量建立的，并在 10 倍交叉验证中进行了验证。
丰富的肿瘤基质和强烈的 α-SMA 表达与总生存（OS）不良相关。然而，在多变量分析中，这两个生物标志物未能对 OS 和无复发生存（RFS）进行分层。不成熟的 FTS 与肿瘤多发性、晚期临床分期以及稀疏的 CD3 和 CD8 阳性肿瘤浸润淋巴细胞（TIL）相关，并且被确定为 OS 和 RFS 的独立预后指标。包含 FTS 成熟度、肿瘤数量、微血管侵犯和淋巴结转移的列线图与传统分期系统相比具有更高的预测能力。
不成熟的 FTS 是生存的独立危险因素，与 ICC 中稀疏的 CD3 和 CD8 阳性 TIL 相关。整合 FTS 成熟度的预后列线图为术后 ICC 患者提供了更准确的风险分层。
越来越多的证据表明，肿瘤微环境（TME）中的纤维成分在 TME 重编程和癌症进展中起着复杂而重要的作用。然而，在临床实践中，对纤维性肿瘤基质（FTS）的评估在某种程度上仍被忽视。本研究表明，在肝内胆管癌（ICC）中，FTS 的组织学成熟度是接受根治性切除的患者的强大预后指标。此外，基于 FTS 成熟度构建的预后列线图与传统的肿瘤-淋巴结-转移分期系统相比具有更高的预测能力。综上所述，在临床常规中应强调 FTS 的评估，以更准确地预测术后 ICC 患者的预后。
