Université Paris Est Créteil, INSERM, IMRB, F-94010 Créteil, France; Assistance Publique-Hôpitaux de Paris, Henri Mondor-Albert Chenevier University Hospital, Department of Pathology, Créteil, France; Inserm, U955, Team 18, Créteil, France; European Reference Network (ERN) RARE-LIVER.
Department of Pathology, Humanitas University, Humanitas Clinical and Research Center, IRCCS, Rozzano, Milan, Italy.
J Hepatol. 2022 Dec;77(6):1586-1597. doi: 10.1016/j.jhep.2022.07.019. Epub 2022 Aug 18.
BACKGROUND & AIMS: Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a rare primary liver cancer (PLC) associated with a poor prognosis. Given the challenges in its identification and its clinical implications, biomarkers are critically needed. We aimed to investigate the diagnostic and prognostic value of the immunohistochemical expression of Nestin, a progenitor cell marker, in a large multicentric series of PLCs.
We collected 461 cHCC-CCA samples from 32 different clinical centers. Control cases included 368 hepatocellular carcinomas (HCCs) and 221 intrahepatic cholangiocarcinomas (iCCAs). Nestin immunohistochemistry was performed on whole tumor sections. Diagnostic and prognostic performances of Nestin expression were determined using receiver-operating characteristic curves and Cox regression modeling.
Nestin was able to distinguish cHCC-CCA from HCC with AUCs of 0.85 and 0.86 on surgical and biopsy samples, respectively. Performance was lower for the distinction of cHCC-CCA from iCCA (AUCs of 0.59 and 0.60). Nestin, however, showed a high prognostic value, allowing identification of the subset of cHCC-CCA ("Nestin High", >30% neoplastic cells with positive staining) associated with the worst clinical outcome (shorter disease-free and overall survival) after surgical resection and liver transplantation, as well as when assessment was performed on biopsies.
We show in different clinical settings that Nestin has diagnostic value and that it is a useful biomarker to identify the subset of cHCC-CCA associated with the worst clinical outcome. Nestin immunohistochemistry may be used to refine risk stratification and improve treatment allocation for patients with this highly aggressive malignancy.
There are different types of primary liver cancers (i.e. cancers that originate in the liver). Accurately identifying a specific subtype of primary liver cancer (and determining its associated prognosis) is important as it can have a major impact on treatment allocation. Herein, we show that a protein called Nestin could be used to refine risk stratification and improve treatment allocation for patients with combined hepatocellular carcinoma, a rare but highly aggressive subtype of primary liver cancer.
混合型肝细胞癌-胆管细胞癌（cHCC-CCA）是一种罕见的原发性肝癌（PLC），预后不良。鉴于其在识别方面的挑战及其临床意义，生物标志物的需求非常迫切。我们旨在通过对来自 32 个不同临床中心的 461 例 cHCC-CCA 样本进行研究，来探究巢蛋白（一种祖细胞标志物）的免疫组化表达在大型多中心 PLC 系列中的诊断和预后价值。
我们收集了 32 个不同临床中心的 461 例 cHCC-CCA 样本。对照病例包括 368 例肝细胞癌（HCC）和 221 例肝内胆管癌（iCCA）。对肿瘤全切片进行巢蛋白免疫组化染色。使用受试者工作特征曲线和 Cox 回归模型确定巢蛋白表达的诊断和预后性能。
巢蛋白能够区分 cHCC-CCA 与 HCC，手术和活检样本的 AUC 分别为 0.85 和 0.86。cHCC-CCA 与 iCCA 的区分性能较低（AUC 分别为 0.59 和 0.60）。然而，巢蛋白具有较高的预后价值，能够识别出与术后和肝移植后最差临床结局相关的 cHCC-CCA 亚组（巢蛋白高表达，>30%肿瘤细胞阳性染色），也能够在活检时评估。
我们在不同的临床环境中表明，巢蛋白具有诊断价值，是一种识别与最差临床结局相关的 cHCC-CCA 亚组的有用生物标志物。巢蛋白免疫组化可能用于细化风险分层，并改善此类高度侵袭性恶性肿瘤患者的治疗分配。
原发性肝癌有不同类型（即起源于肝脏的癌症）。准确识别特定类型的原发性肝癌（并确定其相关预后）非常重要，因为这可能对治疗分配产生重大影响。在此，我们表明，一种称为巢蛋白的蛋白质可用于细化风险分层，并改善此类罕见但高度侵袭性的原发性肝癌——混合型肝细胞癌患者的治疗分配。
