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Tumour epithelial and stromal characteristics of hepatocellular carcinomas with abundant fibrous stroma: fibrolamellar versus scirrhous hepatocellular carcinoma

 Young‐Joo Kim  ;  Hyungjin Rhee  ;  Jeong Eun Yoo  ;  Venancio A F Alves  ;  Gi Jeong Kim  ;  Hye Min Kim  ;  Paulo Herman  ;  Aline Chagas  ;  Haeryoung Kim  ;  Young Nyun Park 
 HISTOPATHOLOGY, Vol.71(2) : 217-226, 2017 
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cancer-associated fibroblast ; fibrolamellar hepatocellular carcinoma ; scirrhous hepatocellular carcinoma ; tumour microenvironment
AIMS: 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.

METHODS AND RESULTS: 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.

CONCLUSION: 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.
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1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Radiology (영상의학교실) > 1. Journal Papers
Yonsei Authors
Kim, Hye Min(김혜민) ORCID logo
Park, Young Nyun(박영년) ORCID logo
Yoo, Jeong Eun(유정은)
Rhee, Hyungjin(이형진) ORCID logo
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