Sarcomatoid hepatocellular carcinoma is distinct from ordinary hepatocellular carcinoma: Clinicopathologic, transcriptomic and immunologic analyses
Sarcomatoid hepatocellular carcinoma is distinct from ordinary hepatocellular carcinoma: Clinicopathologic, transcriptomic and immunologic analyses
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DOI：
10.1002/ijc.33545
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发表时间：
2021-03-13
影响因子：
6.4
通讯作者：
Ochiai, Atsushi
中科院分区：
文献类型：
--
作者：
Morisue, Ryo;Kojima, Motohiro;Ochiai, Atsushi
肉瘤样肝细胞癌是肝细胞癌的一种罕见的组织学亚型，由于缺乏足够的证据将其定义为肝细胞癌的一个亚型，目前被认为是低分化的肝细胞癌。我们的目的是通过综合识别小肝癌与普通肝细胞癌相比的新的和独特的特征来评估将小肝癌分类为肝细胞癌的组织学亚型的可行性。从本院病理数据库(1997-2019年)收录的1106例肝细胞癌中提取15例(1.4%)，其中15例(1.4%)为至少含有10%肉瘤成分的肝细胞癌，15例为与疾病分期随机匹配的肝细胞癌，163例为连续肝细胞癌。小肝癌患者预后不良，根据其他器官肉瘤样癌或未分化癌的不同亚型，可分为多形型、梭形细胞型和巨细胞型。转录分析揭示了小肝癌的明显特征，表现为与上皮向间充质转化和炎症反应相关的基因上调。荧光复合免疫组织化学结果显示，肉瘤样瘤细胞上有明显的程序性死亡配体1(PD-L1)表达，SHC中的CD4(+)和CD8(+)T细胞的浸润率高于OHC。小细胞肺癌非肉瘤成分中CD8(+)T细胞的密度也高于非肉瘤组织。综上所述，本研究的综合分析表明，小肝癌在临床病理、转录本和免疫学特征方面不同于uchC。因此，认为小肝癌是肝细胞癌的一个组织亚型是合理的。
Sarcomatoid hepatocellular carcinoma (SHCC), which was a rare histological subtype of hepatocellular carcinoma (HCC), is currently subclassified as poorly differentiated HCC because of insufficient evidence to define SHCC as a subtype of HCC. We aimed to assess the feasibility of classifying SHCC as a histological subtype of HCC by comprehensively identifying novel and distinct characteristics of SHCC compared to ordinary HCC (OHCC). Fifteen SHCCs (1.4%) defined as HCC with at least a 10% sarcomatous component, 15 randomly disease-stage-matched OHCCs and 163 consecutive OHCCs were extracted from 1106 HCCs in the Pathology Database (1997-2019) of our hospital. SHCC patients showed poor prognosis, and the tumors could be histologically subclassified into the pleomorphic, spindle and giant cell types according to the subtype of carcinomas with sarcomatoid or undifferentiated morphology in other organs. The transcriptomic analysis revealed distinct characteristics of SHCC featuring the upregulation of genes associated with epithelial-to-mesenchymal transition and inflammatory responses. The fluorescent multiplex immunohistochemistry results revealed prominent programmed death-ligand 1 (PD-L1) expression on sarcomatoid tumor cells and higher infiltration of CD4(+) and CD8(+) T cells in SHCCs compared to OHCCs. The density of CD8(+) T cells in the nonsarcomatous component of SHCCs was also higher than that in OHCCs. In conclusion, the comprehensive analyses in our study demonstrated that SHCC is distinct from OHCC in terms of clinicopathologic, transcriptomic and immunologic characteristics. Therefore, it is reasonable to consider SHCC as a histological subtype of HCC.