Background: 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.
Materials and methods: 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.
Results: 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.
Conclusion: 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.
Implications for practice: 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.
摘要
背景。纤维化肿瘤间质 (FTS) 被认为与促进某些肿瘤发展密切相关。在肝内胆管癌 (ICC) 样本的临床常规方面,FTS的组织学特征方便易取。本研究的目标是探求 FTS 的数量及成熟度对外科手术 ICC 患者的预后影响。此外,我们计划为术后 ICC 患者提供一份有效的预后列线图。
材料和方法。回顾性分析连续154位术后 ICC 患者的临床特征。在苏木精和伊红染色的肿瘤切片上对肿瘤间质比率和 FTS 的形态学成熟度进行了评估。在相应的组织微阵列上进行了 CD3、CD8 和 α 平滑肌肌动蛋白 (α‐SMA) 染色。列线图通过多元分析选定的变量制定而成,并经过十倍交叉验证。
结果。丰富的肿瘤基质和较强的 α‐SMA 表达与较差的总生存 (OS) 相关。但是,在多元分析中,这两种生物指标未能将 OS 和无复发生存 (RFS) 分层。未成熟的 FTS 与肿瘤多发率、临床晚期及稀少的 CD3 和 CD8 阳性肿瘤浸润性淋巴细胞 (TIL) 相关,并被认定为 OS 和 RFS 的独立预后指标。与传统的分期系统相比,由 FTS 成熟度、肿瘤数量、微血管侵犯和淋巴结转移组成的列线图具有更高的预测能力。
结论。未成熟的 FTS 是影响生存率的独立危险因素,且与 ICC 中稀少的 CD3 和 CD8 阳性 TIL 相关。整合 FTS 成熟度的预后列线图会为术后 ICC 患者提供更为准确的危险分层
Keywords: Fibrotic tumor stroma; Intrahepatic cholangiocarcinoma; Nomogram; Prognosis.
© AlphaMed Press 2018.