Tumor encapsulation in hepatocellular carcinoma. A pathologic study of 189 cases

Ng, Irene Oi Lin; Lai, Edward C. S.; Fan, Sheung Tat; Ng, Matthew

doi:10.1002/1097-0142(19920701)70:1<45::aid-cncr2820700108>3.0.co;2-7

Cited by 170 publications

(111 citation statements)

References 13 publications

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“…34 Conversely, MMP2, MT1-MMP, and TIMP2 mRNA levels in nontumor livers were not correlated with the presence or absence of capsule (not shown), consistent with the previous demonstration that tumor encapsulation was independent of the cirrhotic process. 34 MMP2 activities in HCCs and matching nontumor livers were correlated. In addition, MMP2 activity was higher in tumors arising in cirrhotic livers than in those arising in noncirrhotic livers, and it was associated with the stage of fibrosis.…”

Section: Discussionsupporting

confidence: 90%

Increased extracellular matrix remodeling is associated with tumor progression in human hepatocellular carcinomas

Théret¹

2001

Hepatology

182

128

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Matrix metalloproteinase-2 (MMP2) is a key enzyme in the process of extracellular matrix remodeling involved in tumor invasion and metastasis. The activation of MMP2 involves interplay with the membrane type-matrix metalloproteinase-1 (MT1-MMP) and the tissue inhibitor of metalloproteinase-2 (TIMP2). In vitro, activated hepatic stellate cells are a main source of MMP2 and collagen I induces MMP2 activation. The steady-state mRNA levels of MMP2, MT1-MMP, TIMP2, collagen I, collagen IV, and laminin ␥1 were compared with MMP2 activity in 55 hepatocellular carcinomas, 47 matching nontumor biopsies and 19 histologically normal livers. In hepatocellular carcinomas, increased collagen I mRNA levels were strongly associated with those of MMP2 (Spearman R ‫؍‬ .74, P < .001), MT1-MMP (R ‫؍‬ .65, P < .001) and TIMP2 (R ‫؍‬ 0.61, P < .001). MMP2 activity was correlated with the mRNA expression of collagen I (R ‫؍‬ .45 P < .01), collagen IV (R ‫؍‬ .40, P < .01) and laminin ␥1 (R ‫؍‬ .33, P < .05). Unlike collagen IV and laminin ␥1 mRNAs, MMP2, MT1-MMP, TIMP2, collagen I mRNA levels were increased in nonencapsulated compared with encapsulated tumors (P < .05). In addition, MMP2 activity was fourfold higher (P < .01) in tumors arising in cirrhotic livers than in those arising in noncirrhotic livers. Moreover, tumor recurrence was associated with 4.6-and 2.8-fold (P < .05) higher collagen I and MMP2 mRNA levels, respectively, in hepatocellular carcinomas arising in cirrhotic livers. Thus, a high extracellular matrix remodeling favors tumor progression in hepatocellular carcinomas. (HEPATOLOGY 2001;34:82-88.)Tumor progression depends on the interplay between transformed cells and their micro-environment, particularly the surrounding extracellular matrix (ECM). 1 The balance between synthesis and degradation of ECM components is indeed a key modulator of tumor growth and metastasis. Among the proteases involved in the turnover of ECM, matrix metalloproteinase 2 (MMP2), the type IV collagenase/gelatinase, was shown to specifically act in the process of basementmembrane remodeling related to tumor progression. 2 MMP2 is secreted as a proenzyme and the critical step of MMP2 activation occurs at the cell surface through the formation of a molecular complex involving MMP2, the membrane-type matrix metalloproteinase MT1-MMP 3 and the tissue inhibitor of MMP2, TIMP2, which promotes the binding of MT1-MMP to MMP2. 4 Thus, TIMP2 plays a dual role by acting at a high concentration as a specific inhibitor of MMP2 activation and at a low concentration as a trigger of MMP2 and MT1-MMP clustering. 5 In human livers, fibrogenesis underlies the development of HCC in at least 90% of cases and HCC is an ominous complication of cirrhosis in 30% of the patients. 6,7 However, direct relationships between fibrosis and the progression of HCC were not shown, so far. Increased expression of MMP2, tissue inhibitors of metalloproteinase (TIMP1 and TIMP2), and MT1-MMP by nonparenchymal cells were reported in fibrosis 8-9 and in HCC. [10][11][12] Indeed, hep...

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Section: Discussionsupporting

confidence: 90%

Increased extracellular matrix remodeling is associated with tumor progression in human hepatocellular carcinomas

Théret¹

2001

Hepatology

182

128

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“…These groups of patients usually have a poor disease outcome, which is in agreement with our current observation. 43 In conclusion, the high expression of CYP2E1 in adjacent nontumor tissue may play an important role in HCC carcinogenesis through metabolizing procarcinogens and generating reactive oxygen species. The low level of CYP2E1 in tumor tissue, which was found in patients with more aggressive type of tumor and poor prognosis, may allow the rapid proliferation of the tumor cells by escaping the cytotoxicity generated by CYP2E1.…”

Section: Cyp2e1 Protein Expression and Clinicopathological Features Omentioning

confidence: 97%

Decreased expression of cytochrome P450 2E1 is associated with poor prognosis of hepatocellular carcinoma

Cheung

Leung

et al. 2004

Intl Journal of Cancer

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“…Encapsulated HCCs appear to be less aggressively invasive than tumours without this feature. 129 Vascular invasion is valued as an early indicator of the aggressiveness of a tumour (for example, its metastatic potential or the likelihood of rapid recurrence following treatment). 130 Rates of vascular invasion are significantly lower in tumours that are small, 131 histologically well differentiated 132 or encapsulated.…”

Section: Pathologymentioning

confidence: 99%

“…130 Rates of vascular invasion are significantly lower in tumours that are small, 131 histologically well differentiated 132 or encapsulated. 129 It has also been found that tumours arising in women are more likely to be encapsulated 133 and less likely to show vascular invasion.…”

Section: Pathologymentioning

confidence: 99%

See 1 more Smart Citation

Surveillance of cirrhosis for hepatocellular carcinoma: systematic review and economic analysis

Coon¹,

Rogers²,

Hewson³

et al. 2007

Health Technol Assess

150

108

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Tumor encapsulation in hepatocellular carcinoma. A pathologic study of 189 cases

Cited by 170 publications

References 13 publications

Increased extracellular matrix remodeling is associated with tumor progression in human hepatocellular carcinomas

Increased extracellular matrix remodeling is associated with tumor progression in human hepatocellular carcinomas

Decreased expression of cytochrome P450 2E1 is associated with poor prognosis of hepatocellular carcinoma

Surveillance of cirrhosis for hepatocellular carcinoma: systematic review and economic analysis

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