Cd44 Is Expressed in Hepatocellular Carcinomas Showing Vascular Invasion

Mathew, Joseph; Hines, Julie E.; Obafunwa, John Oladapo; Burr, Andrew; Toole, Kieran; Burt, Alastair D.

doi:10.1002/(sici)1096-9896(199605)179:1<74::aid-path531>3.0.co;2-e

Cited by 55 publications

(21 citation statements)

References 17 publications

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“…However, they used a monoclonal antibody (A3D8) that could not discriminate between CD44s and CD44v. 43 Mathew et al 42 mentioned that CD44s, CD44v3, and CD44v6 were not expressed by hepatocytes or biliary cells. In the present study, we could examine immunoreactivity of at least five CD44 isoforms in normal livers.…”

Section: Discussionmentioning

confidence: 99%

“…38,39 In animal experiment, transfection of complementary DNA (CD44v6) into a non-metastasizing rat pancreatic carcinoma cell line conferred metastasizing properties to the cell line 40 ; pretreatment of anti-CD44 was subsequently shown to retard or prevent metastasis formation. 41 In the liver malignancies, CD44 expression in HCC has been studied by Mathew et al 42 and Washington et al 43 ; however, CD44 expression has rarely been examined in CC.…”

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confidence: 99%

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Expression of e-cadherin, ?-catenin, ?-catenin, and CD44 (standard and variant isoforms) in human cholangiocarcinoma: An immunohistochemical study

et al. 1998

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Immunolocalization of E-cadherin (E-cad), ␣-catenin, ␤-catenin, and CD44 has rarely been investigated in human cholangiocarcinoma (CC). We, therefore, immunohistochemically examined the expression of E-cad, ␣-catenin, ␤-catenin, CD44 standard (CD44s), and CD44 variants (CD44v) including CD44v5, CD44v6, CD44v7-8, and CD44v10 in normal adult livers and in 47 cases of CC; and the results were then correlated with tumor grade, vascular invasion, metastasis, p53 expression, proliferative fraction (Ki-67 labeling), and c-erbB2 expression. In normal livers, E-cad, ␣-catenin and ␤-catenin, but not CD44s, CD44v5, CD44v6, CD44v7-8, and CD44v10, were expressed at the cell membrane of normal intrahepatic bile ducts. In CC, membranous expression of E-cad, ␣-catenin, and ␤-catenin was the same or reduced when compared with noncancerous bile ducts in the majority of CC. We found that the down-regulation of E-cad, ␣-catenin, and ␤-catenin expression significantly correlated with tumor high grade, but not with vascular invasion, metastasis, p53 expression, Ki-67 labeling, or c-erbB2 expression, except for ␤-catenin, the down-regulation of which was associated with c-erbB2 down-regulation. CD44s, CD44v5, CD44v6, CD44v7-8 and CD44v10 were frequently expressed at the membrane of CC cells. There were, however, no significant correlations between these aberrant CD44 expression and tumor grade, metastasis, vascular invasion, p53 expression, Ki-67 labeling, or c-erbB2 expression, with a few exceptions of CD44s and CD44v5. We found that CD44s aberrant expression significantly correlated with absence of metastasis and vascular invasion, and that CD44v5 aberrant expression significantly correlated with p53 under-expression. These results suggest that membranous expression of E-cad, ␣-catenin, and ␤-catenin is reduced in a majority of CC and this down-regulation correlates with CC high grade, and that ␤-catenin down-regulation is associated with c-erbB2 down-regulation. The data also suggested that CD44s, CD44v5, CD44v6, CD44v7-8, and CD44v10 may be neoexpressed during carcinogenesis of CC but this neoexpression does not correlate with tumor progression in CC, with the exception of CD44s and CD44v5. (HEPATOLOGY 1998;27:974-982.)

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Expression of e-cadherin, ?-catenin, ?-catenin, and CD44 (standard and variant isoforms) in human cholangiocarcinoma: An immunohistochemical study

et al. 1998

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“…Ezrin is capable of interacting with several previously identified metastasis‐associated molecules 3, 4. Among the molecules, CD44 and c‐Met/hepatocyte growth factor (HGF) receptor are cell‐surface molecules known to be implicated in metastasis and progression of HCC 20, 21. E‐cadherin is an adhesion molecule also known to interact with ezrin and its downregulation has been associated with malignant progression of HCC 22.…”

Section: Introductionmentioning

confidence: 99%

Prognostic implications of ezrin expression in human hepatocellular carcinoma

Kang

Hong

Lee

et al. 2010

Molecular Carcinogenesis

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Ezrin is known to regulate cellular survival, adhesion, migration, and invasion and has been identified as one of the key components of tumor progression and metastasis. The authors investigated ezrin expression in human hepatocellular carcinoma (HCC) and sought to determine its relation with clinicopathologic parameters, patients' outcome, and interacting molecular markers. Ezrin expression was assessed by immunohistochemical staining in 100 surgically resected HCCs using the tissue microarray method. A total of 28 HCCs showed high ezrin immunoreactivity, mainly in cytoplasm. Ezrin expression exhibited a positive correlation with c-Met expression (P = 0.001), but showed no correlation with the expression of CD44s or E-cadherin. HCCs expressing high level of ezrin were significantly associated with advanced TNM stage, poor Edmondson's histological grade, macroscopic portal vein invasion, tumor recurrence, and extrahepatic recurrence (P < 0.05). Univariate analysis showed that HCCs with high ezrin immunoreactivity were strongly associated with unfavorable overall and disease-free survivals than HCCs with low or negative for ezrin immunoreactivity (P = 0.0001 and 0.0011, respectively). Furthermore, multivariate analysis demonstrated that a high level of ezrin expression was independently associated with poor overall survival (hazard ratio, 1.905; P = 0.011). The results suggest that ezrin expression could be a potential predictive marker of progression, metastasis, and prognosis in HCC.

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“…Studies focusing primarily on new prognostic markers have been based on small numbers of patients, did not use an identically treated patient group, or emphasized clinical parameters only. [3][4][5] Pathological parameters were neither examined in detail, nor compared with possible new prognostic factors. 6 Moreover, potential prognostic indicators have been investigated almost exclusively in Asian rather than western medical centres.…”

Section: Introductionmentioning

confidence: 99%

Apoptosis and proliferation in relation to histopathological variables and prognosis in hepatocellular carcinoma

et al. 1999

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The prognosis of patients with resectable hepatocellular carcinoma depends mainly on the anatomical extent of the tumour and on the general condition of the patient. Given the growing evidence that proliferation indices may be of prognostic significance in hepatocellular carcinomas and that parameters of cell loss (usually, but not exclusively, due to programmed cell death) are biologically relevant, the identification and quantitation of proliferative capacity and apoptosis may be of prognostic importance. In this study four different methods have been used to assess proliferation in a series of 193 curatively (R0) resected hepatocellular carcinomas: mitotic count, immunohistochemical assessment of MIB‐1 (Ki‐67), proliferating cell nuclear antigen (PCNA), and silver‐stained nucleolar organizer regions (AgNORs). Apoptosis was assessed using the in situ‐end labelling (ISEL) technique in combination with morphological criteria. Patients who received liver transplantation were excluded. The results obtained were compared with histopathological stage (according to UICC), Edmondson grade, several other histopathological factors, and survival rate. Significant statistical correlations were seen between the mitotic index, the rate of nuclear positivity for MIB‐1 and PCNA, and the number of AgNOR dots. In univariate survival analysis, tumour stage and Edmondson grade, mitotic index, MIB‐1 and PCNA index, and mean AgNOR number were significant factors influencing patients' survival. On multivariate Cox survival analysis, mitotix index, concomitant cirrhosis, Edmondson grade, and patient age were the only significant independent prognostic factors. Apoptosis was not related to prognosis or to other parameters examined. These results indicated that mitotic index is an additional prognostic parameter which could provide auxiliary information for patients' outcome. MIB‐1 and PCNA immunostaining and AgNORs showed a good correlation among themselves. Apoptosis did not predict prognosis in hepatocellular carcinoma. Copyright © 1999 John Wiley & Sons, Ltd.

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Cd44 Is Expressed in Hepatocellular Carcinomas Showing Vascular Invasion

Cited by 55 publications

References 17 publications

Expression of e-cadherin, ?-catenin, ?-catenin, and CD44 (standard and variant isoforms) in human cholangiocarcinoma: An immunohistochemical study

Expression of e-cadherin, ?-catenin, ?-catenin, and CD44 (standard and variant isoforms) in human cholangiocarcinoma: An immunohistochemical study

Prognostic implications of ezrin expression in human hepatocellular carcinoma

Apoptosis and proliferation in relation to histopathological variables and prognosis in hepatocellular carcinoma

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