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Tumour epithelial and stromal characteristics of hepatocellular carcinomas with abundant fibrous stroma: fibrolamellar versus scirrhous hepatocellular carcinoma
Author(s) -
Kim YoungJoo,
Rhee Hyungjin,
Yoo Jeong Eun,
Alves Venancio A F,
Kim Gi Jeong,
Kim Hye Min,
Herman Paulo,
Chagas Aline,
Kim Haeryoung,
Park Young Nyun
Publication year - 2017
Publication title -
histopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.626
H-Index - 124
eISSN - 1365-2559
pISSN - 0309-0167
DOI - 10.1111/his.13219
Subject(s) - hepatocellular carcinoma , stroma , immunohistochemistry , pathology , medicine , stromal cell , carcinoma , cancer research
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‐ HCC s and 9 FL ‐ HCC s were subjected to immunohistochemical stains for keratin 7 (K7), K19, Ep CAM , CD 56/ NCAM , CD 163, CD 68, pSTAT 3, FAP , CCN 2 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 . CD 68 and CD 163‐positive tumour‐infiltrating macrophages, and FAP ‐positive cancer‐associated fibroblasts ( CAF s) were more abundant in the stroma of S‐ HCC s compared to FL ‐ HCC s (all P < 0.05). Tumour epithelial K19 expression was more frequent in S‐ HCC s compared to FL ‐ HCC s ( P = 0.023). Significant positive correlations were seen between pSTAT 3 expression status in tumour epithelial cells and CAF s, the extent of stromal CAF and macrophage infiltration and K19 expression status. No significant differences were seen for K7, Ep CAM , CD 56/ NCAM , CCN 2 expression and Ki‐67 labelling index between S‐ HCC s and FL ‐ HCC s. 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.