Kim Young-Joo, Rhee Hyungjin, Yoo Jeong Eun, Alves Venancio A F, Kim Gi Jeong, Kim Hye Min, Herman Paulo, Chagas Aline, Kim Haeryoung, Park Young Nyun
Department of Pathology, Brain Korea 21 PLUS Project for Medical Science, Integrated Genomic Research Center for Metabolic Regulation, Yonsei University College of Medicine, Seoul, Korea.
Department of Pathology, University of São Paulo School of Medicine, São Paulo, Brazil.
Histopathology. 2017 Aug;71(2):217-226. doi: 10.1111/his.13219. Epub 2017 May 22.
The scirrhous variant of hepatocellular carcinoma (S-HCC) and fibrolamellar HCC (FL-HCC) are less common subtypes of HCC that are characterized by abundant fibrous stroma. Here, we aimed to investigate differences in the tumour microenvironment and the tumour epithelial cell characteristics of S-HCC and FL-HCC.
Whole tissue sections of 17 S-HCCs and 9 FL-HCCs were subjected to immunohistochemical stains for keratin 7 (K7), K19, EpCAM, CD56/NCAM, CD163, CD68, pSTAT3, FAP, CCN2 and Ki-67. FL-HCC patients were younger than S-HCC patients (P < 0.001), and chronic liver disease was seen in the background of 88.2% of S-HCC and in none of the FL-HCC. CD68 and CD163-positive tumour-infiltrating macrophages, and FAP-positive cancer-associated fibroblasts (CAFs) were more abundant in the stroma of S-HCCs compared to FL-HCCs (all P < 0.05). Tumour epithelial K19 expression was more frequent in S-HCCs compared to FL-HCCs (P = 0.023). Significant positive correlations were seen between pSTAT3 expression status in tumour epithelial cells and CAFs, the extent of stromal CAF and macrophage infiltration and K19 expression status. No significant differences were seen for K7, EpCAM, CD56/NCAM, CCN2 expression and Ki-67 labelling index between S-HCCs and FL-HCCs.
S-HCC and FL-HCC are subtypes of HCC with extensive fibrosis, and the nature of the fibrous stroma differs between them. While the stroma of FL-HCC is composed of dense lamellated collagenous bands with sparse cellular components, S-HCC demonstrates more abundant CAF and tumour-infiltrating macrophages and stemness-related marker expression, suggesting the presence of a complex tumour microenvironment that may influence the aggressive behaviour of S-HCCs.
肝细胞癌的硬化型（S-HCC）和纤维板层型肝癌（FL-HCC）是肝癌中较罕见的亚型，其特征为富含纤维基质。在此，我们旨在研究S-HCC和FL-HCC在肿瘤微环境及肿瘤上皮细胞特征方面的差异。
对17例S-HCC和9例FL-HCC的全组织切片进行角蛋白7（K7）、K19、上皮细胞黏附分子（EpCAM）、CD56/神经细胞黏附分子（NCAM）、CD163、CD68、磷酸化信号转导和转录激活因子3（pSTAT3）、成纤维细胞活化蛋白（FAP）、结缔组织生长因子（CCN2）和Ki-67的免疫组化染色。FL-HCC患者比S-HCC患者年轻（P<0.001），88.2%的S-HCC有慢性肝病背景，而FL-HCC均无。与FL-HCC相比，S-HCC基质中CD68和CD163阳性的肿瘤浸润巨噬细胞以及FAP阳性的癌症相关成纤维细胞（CAF）更为丰富（所有P<0.05）。与FL-HCC相比，S-HCC中肿瘤上皮K19表达更常见（P=0.023）。肿瘤上皮细胞和CAF中pSTAT3表达状态、基质CAF和巨噬细胞浸润程度与K19表达状态之间存在显著正相关。S-HCC和FL-HCC之间K7、EpCAM、CD56/NCAM、CCN2表达及Ki-67标记指数无显著差异。
S-HCC和FL-HCC是具有广泛纤维化的肝癌亚型，它们之间纤维基质的性质不同。虽然FL-HCC的基质由致密的板层状胶原带和稀疏的细胞成分组成，但S-HCC显示出更丰富的CAF和肿瘤浸润巨噬细胞以及干性相关标志物表达，提示存在可能影响S-HCC侵袭行为的复杂肿瘤微环境。
