Combined hepatocellular and cholangiocarcinoma originating from the same clone: a pathomolecular evidence-based study.
Combined hepatocellular and cholangiocarcinoma originating from the same clone: a pathomolecular evidence-based study.
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源自同一克隆的合并肝细胞癌和胆管癌：一项病理分子循证研究
DOI：
10.1186/s40880-016-0146-7
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发表时间：
2016-08-24
影响因子：
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通讯作者：
Wu MC
中科院分区：
文献类型：
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作者：
Zhao Q;Yu WL;Lu XY;Dong H;Gu YJ;Sheng X;Cong WM;Wu MC
肝细胞胆管癌（CHC）是肝癌的一种独特亚型，包括肝细胞癌（HCC）和肝内胆管癌（ICC）；然而，其细胞起源仍不清楚。本研究的目的是探讨 34 例 CHC 患者的临床病理特征以及 HCC 与 ICC 的克隆关系。将34例CHC患者的临床病理特征和预后与29例分离的HCC和ICC（SHC）患者进行比较。在 16 个 CHC 和 10 个 SHC 组织中检测到 10 个高度多态性微卫星标记的杂合性丢失 (LOH)，以确定 CHC 的克隆起源。通过免疫组织化学分析检测肿瘤组织中肝细胞标志物[肝细胞石蜡1（Hep Par 1）和磷脂酰肌醇蛋白聚糖3（GPC3）]和胆管细胞标志物[细胞角蛋白（CK）7和19]的表达。在16个CHC标本中，HCC和ICC之间的LOH模式差异小于30%，表明HCC和ICC具有相同的克隆起源。与这一发现一致的是，免疫组织化学分析显示，52.9% CHC 标本的 HCC 和 ICC 成分中同时表达肝细胞标记物（Hep Par 1 和 GPC3）和胆管细胞标记物（CK7 和 CK19），表明这两种成分与肝祖细胞 (HPC) 具有相似的表型。相反，在所有 10 例 SHC 病例中，HCC 和 ICC 成分之间的 LOH 模式差异大于 30%，表明 HCC 和 ICC 的克隆起源不同。 CHC 患者的总生存期和无病生存期短于 SHC 患者 (P < 0.05)。我们的结果表明，CHC 的 HCC 和 ICC 成分可能源自同一克隆，具有类似于 HPC 的双向分化潜力。 CHC往往表现出HCC和ICC的生物学行为，这可能增强肿瘤细胞的浸润能力，导致CHC患者的临床结果不佳。
Combined hepatocellular and cholangiocarcinoma (CHC) is a unique subtype of liver cancer comprising both hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC); however, its cellular origin remains unclear. The purpose of this study was to investigate the clinicopathologic features and the clonal relationship between HCC and ICC in 34 patients with CHC. The clinicopathologic features and prognosis of the 34 CHC patients were compared with those of 29 patients with separated HCC and ICC (SHC). Loss of heterozygosity (LOH) at 10 highly polymorphic microsatellite markers was detected in 16 CHC and 10 SHC tissues for determination of the clonal origin of CHC. Expression of hepatocyte markers [hepatocyte paraffin 1 (Hep Par 1) and glypican 3 (GPC3)] and cholangiocyte markers [cytokeratin (CK)7 and 19] in tumor tissues was examined by immuno histochemical analysis. In the 16 CHC specimens, the difference in LOH patterns between HCC and ICC was less than 30%, suggesting the same clonal origin of HCC and ICC. Consistent with this finding, immunohistochemical analysis revealed that hepatocyte markers (Hep Par 1 and GPC3) and cholangiocyte markers (CK7 and CK19) were simultaneously expressed in both the HCC and ICC components in 52.9% of CHC specimens, suggesting that the two components shared a similar phenotype with hepatic progenitor cells (HPCs). On the contrary, in all 10 SHC cases, the difference in LOH patterns between the HCC and ICC components was greater than 30%, suggesting different clonal origins of HCC and ICC. Overall survival and disease-free survival were shorter for patients with CHC than for patients with SHC (P < 0.05). Our results suggest that the HCC and ICC components of CHC may originate from the same clone, having the potential for dual-directional differentiation similar to HPCs. CHC tended to exhibit the biological behaviors of both HCC and ICC, which may enhance the infiltrative capacity of tumor cells, leading to poor clinical outcomes for patients with CHC.