Morphophenotypic changes in human multistep hepatocarcinogenesis with translational implications

Sciarra, Amedeo; Tommaso, Luca Di; Nakano, Masayuki; Destro, Annarita; Torzilli, Guido; Donadon, Matteo; Maggioni, Marco; Bòsari, Silvano; Bulfamante, Gaetano; Matsuda, Masanori; Fujii, Hideki; Ichikawa, Tomoaki; Morisaka, Hiroyuki; Sano, Katsuhiro; Ichikawa, Shintaro; Roncalli, Massimo

doi:10.1016/j.jhep.2015.08.031

Cited by 42 publications

(42 citation statements)

References 22 publications

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“…Interestingly, the PTH lesion in this patient showed characteristics similar to premalignant transformation with phenotype alterations reported in early hepatocellular carcinoma (HCC) 10. NASH is a leading cause of cirrhosis and has been associated with the development of HCC 11,12.…”

Section: Discussionsupporting

confidence: 58%

Peritumoral Hyperplasia in Hepatic Sclerosed Hemangioma

Shimada

Tajiri

Baba

et al. 2017

ACG Case Reports Journal

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Peritumoral hyperplasia (PTH) is a hyperplastic lesion located around hypervascular tumors. Hepatic sclerosed hemangioma is a very rare form of hemangioma with sclerotic changes and is distinct from sclerosing hemangioma. We present a patient with non-alcoholic steatohepatitis-induced cirrhosis who presented with a hypervascular tumor. The tumor showed atypical findings of hemangioma and was treated with surgical resection because hepatic malignancy could not be ruled out. Histopathologic examination revealed the tumor was a sclerosed hemangioma with PTH. Lesions with carcinogenic potential were found in the PTH lesion. Sclerosed hemangioma should be observed and managed carefully.

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Section: Discussionsupporting

confidence: 58%

Peritumoral Hyperplasia in Hepatic Sclerosed Hemangioma

Shimada

Tajiri

Baba

et al. 2017

ACG Case Reports Journal

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“…reported for the first time that the expression of GS in HCC tissue is higher than that in para‐tumor tissue . The expression level of GS elevates gradually during malignant transformation of hepatic lesion and progression of HCC . GS is a target of the Wnt/beta‐catenin signal pathway in the liver, and the expression of GS is regulated by translocation of beta‐catenin from the cytoplasm to the cell nucleus, which indicates the activation of the Wnt/beta‐catenin signal pathway .…”

Section: Introductionmentioning

confidence: 98%

Glutamine synthetase promotes tumor invasion in hepatocellular carcinoma through mediating epithelial–mesenchymal transition

Liu

Al-Ameri

et al. 2020

Hepatology Research

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Aim Glutamine synthetase (GS) levels increase gradually with the development of hepatocellular carcinogenesis. In this study, we aimed to investigate the clinical significance of GS and the underlying mechanism of GS promoting hepatocellular carcinoma (HCC) invasion. Methods Serum concentration of GS and α‐fetoprotein (AFP) in HCC patients, liver cirrhosis patients, and healthy individuals were detected. The GS‐mRNA level and its prognostic value were explored in an independent HCC cohort from The Cancer Genome Atlas database. GS expression in HCC tissue and matched para‐tumor tissue was determined. The effect of GS on HCC invasion was assessed in vitro and in vivo. Results The serum GS and AFP level in HCC patients was higher than that in healthy controls and liver cirrhosis patients. The area under the receiver operating characteristic curve for HCC diagnosis was 0.848 and 0.861 for GS and AFP, respectively. The area under the receiver operating characteristic curve of GS for diagnosis of AFP‐negative HCC was 0.913. Combining GS with AFP achieved a diagnostic sensitivity and specificity of 82.5% and 93%, respectively. The GS level was higher in tumor tissues than that in para‐tumor tissues. High GS expression was associated with poor prognosis of moderately differentiated HCC patients. In vitro, GS exerted an influence on HCC cell migration by mediating epithelial–mesenchymal transition. The lung and liver metastatic model of HCC further confirmed that GS expression affected the invasion of HCC cells in vivo. Conclusions GS is a useful biomarker for HCC diagnosis, especially for AFP‐negative patients. In addition, GS affects HCC metastasis through mediating epithelial–mesenchymal transition.

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“…Sinusoid capillarisation, indicated by CD34 staining, is useful for differentiating HGDN, eHCC and pHCC 14. A recent study showed neoangiogenesis can provide complementary and very useful information for deciphering the biology of individual HCCs 15.…”

Section: Discussionmentioning

confidence: 99%

Stromal morphological changes and immunophenotypic features of precancerous lesions and hepatocellular carcinoma

et al. 2019

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AimsTo evaluate stromal histopathological features and immunostaining expression for differential diagnosis of low- and high-grade dysplastic nodules (HGDN) to early and progressed hepatocellular carcinomas (eHCC, pHCC).MaterialsWe evaluated sinusoid capillarisation (SC), solitary artery (SA), ductular reaction (DR), stromal invasion and expression of six biomarkers (GPC3, HSP70, GS, CD34, CK19, EpCAM) in a series of 97 cases.ResultsStromal morphological changes, including SC, DR and SA, exhibited significant differences in differential diagnosis. In one indicator, SC had the best sensitivity (90.00%) and accuracy (85.42%), and SA had the best specificity at 88.89 %. In combinations, SC +and SA +were favourable and optimal. The immunoreactivity of GPC3, HSP70 and GS increased significantly in line with the stepwise progression of hepatocarcinogenesis.ConclusionsStromal histopathology features are useful for diagnosing HGDN, eHCC and small HCC. The immunostaining panel of GPC3, HSP70 and GS can also be supplementary.

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Morphophenotypic changes in human multistep hepatocarcinogenesis with translational implications

Cited by 42 publications

References 22 publications

Peritumoral Hyperplasia in Hepatic Sclerosed Hemangioma

Peritumoral Hyperplasia in Hepatic Sclerosed Hemangioma

Glutamine synthetase promotes tumor invasion in hepatocellular carcinoma through mediating epithelial–mesenchymal transition

Stromal morphological changes and immunophenotypic features of precancerous lesions and hepatocellular carcinoma

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