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Lung and lymph node metastases from hepatocellular carcinoma: Comparison of pathological aspects

Authors
 Ha Young Woo  ;  Hyungjin Rhee  ;  Jeong Eun Yoo  ;  Se Hoon Kim  ;  Gi Hong Choi  ;  Do Young Kim  ;  Hyun Goo Woo  ;  Hye Sun Lee  ;  Young Nyun Park 
Citation
 LIVER INTERNATIONAL, Vol.42(1) : 199-209, 2022-01 
Journal Title
LIVER INTERNATIONAL
ISSN
 1478-3223 
Issue Date
2022-01
MeSH
Carcinoma, Hepatocellular* / pathology ; Epithelial-Mesenchymal Transition ; Humans ; Liver Neoplasms* / pathology ; Lung ; Lymphatic Metastasis
Keywords
epithelial-mesenchymal transition ; extrahepatic metastasis ; hepatocellular carcinoma ; keratin 19 ; macrotrabecular-massive ; vessels encapsulating tumour clusters
Abstract
Background & aims: Extrahepatic metastasis from hepatocellular carcinoma (HCC) is a catastrophic event, yet organ-specific pathological characteristics of metastatic HCC remain unclear. We aimed to characterize the pathological aspects of HCC metastases to various organs.

Methods: We collected intrahepatic HCC (cohort 1, n = 322) and extrahepatic metastatic HCC (cohort 2, n = 130) samples. Clinicopathological evaluation and immunostaining for K19, CD34, αSMA, fibroblast-associated protein (FAP), CAIX, VEGF, PD-L1, CD3, CD8, Foxp3, CD163 and epithelial-mesenchymal transition (EMT)-related markers were performed.

Results: Independent factors for extrahepatic metastasis included BCLC stage B-C, microvascular invasion (MVI), vessels encapsulating tumour clusters (VETC)-HCC, K19 and FAP expression, and CD163+ macrophage infiltration (cohort 1, P < .05 for all). Lung metastases (n = 63) had the highest proportion of VETC-HCC and macrotrabecular-massive (MTM)-HCC. Lymph node metastases (n = 19) showed significantly high rates of EMT-high features, K19 expression, fibrous tumour stroma with αSMA and FAP expression, high immune cell infiltration, PD-L1 expression (combined positive score), CD3+, CD8+, Foxp3+ T cell and CD163+ macrophage infiltration (adjusted P < .05 for all). In both cohorts, EMT-high HCCs showed higher rates of K19 expression, fibrous tumour stroma, high immune cell infiltration, PD-L1 expression and CD3+ T cell infiltration, whereas EMT-low HCCs were more frequent among VETC-HCCs (P < .05 for all). Overall phenotypic features were not significantly different between paired primary-metastatic HCCs (n = 32).

Conclusions: Metastatic HCCs to various organs showed different pathological features. VETC and MTM subtypes were related to lung metastasis, whereas K19 expression, EMT-high features with fibrous tumour stroma and high immune cell infiltration were related to lymph node metastasis.
Full Text
https://onlinelibrary.wiley.com/doi/10.1111/liv.15051
DOI
10.1111/liv.15051
Appears in Collections:
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 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
1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
Yonsei Authors
Kim, Do Young(김도영)
Kim, Se Hoon(김세훈) ORCID logo https://orcid.org/0000-0001-7516-7372
Park, Young Nyun(박영년) ORCID logo https://orcid.org/0000-0003-0357-7967
Woo, Ha Young(우하영) ORCID logo https://orcid.org/0000-0002-3078-6484
Yoo, Jeong Eun(유정은) ORCID logo https://orcid.org/0000-0001-9990-279X
Rhee, Hyungjin(이형진) ORCID logo https://orcid.org/0000-0001-7759-4458
Lee, Hye Sun(이혜선) ORCID logo https://orcid.org/0000-0001-6328-6948
Choi, Gi Hong(최기홍) ORCID logo https://orcid.org/0000-0002-1593-3773
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/187859
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