Ezrin immunoreactivity in relation to survival in serous ovarian carcinoma patients

Moilanen, J.; Lassus, Heini; Leminen, Arto; Vaheri, Antti; Bützow, Ralf; Carpén, Olli

doi:10.1016/s0090-8258(03)00262-2

Cited by 79 publications

(62 citation statements)

References 20 publications

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“…Ezrin Expression in Esophageal Carcinoma was associated with shorter survival and a higher histological grade of the disease (Moilanen et al 2003). However, we could not find a significant correlation between ezrin expression level and the clinical parameters.…”

Section: The Journal Of Histochemistry and Cytochemistrycontrasting

confidence: 84%

“…Evidence suggested that ezrin was downregulated and played a suppressive role in tumor progression (Tokunou et al 2000;Guan et al 2002;Moilanen et al 2003). Our present study showed that ezrin protein expression level in normal esophageal epithelium was higher than in ESCC in 73.5% of the 49 samples.…”

Section: Discussionsupporting

confidence: 50%

“…PCNA expression level was higher in the group of ezrin T/N ratio ,1.0 than in the group of ezrin T/N ratio .1.0. structures were either negative or diffusely positive for ezrin in the cytoplasm. Moilanen et al (2003) also described the subcellular redistribution of ezrin in serous ovarian carcinoma. Similarly, we found an obvious translocation of ezrin from membrane to the cytoplasm during the development of ESCC.…”

Section: Discussionmentioning

confidence: 99%

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Altered Expression of Ezrin in Esophageal Squamous Cell Carcinoma

Zeng

et al. 2006

J Histochem Cytochem.

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Ezrin is a membrane-cytoskeletal linker belonging to the ezrin-radixin-moesin (ERM) family and has been suggested to be involved in tumorigenesis. In this study we investigated ezrin expression pattern in normal esophageal mucosa and esophageal squamous cell carcinoma (ESCC) and the correlation with clinical characteristics. Immunohistochemical staining showed a tendency for ezrin to translocate from membrane to cytoplasm in the progression from normal epithelium to invasive carcinoma of the esophagus. By Western blot, we found that ezrin expression was downregulated in 13 ESCC specimens and upregulated in 36 others. Moreover, quantitative real-time RT-PCR demonstrated that ezrin mRNA level in normal esophageal mucosa was 3.60 ± 3.60 times that in ESCC ( p<0.001). Proliferating cell nuclear antigen (PCNA) expression level was higher in ezrin downregulated group compared with that in ezrin upregulated group ( p<0.05). However, there was no significant association between ezrin expression and clinical characteristics. The results suggested that the localization of ezrin by immunohistochemistry may be useful in the diagnosis of ESCC, and ezrin may play a suppressive role in the tumorgenesis of ESCC.

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Section: The Journal Of Histochemistry and Cytochemistrycontrasting

confidence: 84%

Section: Discussionsupporting

confidence: 50%

Section: Discussionmentioning

confidence: 99%

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Altered Expression of Ezrin in Esophageal Squamous Cell Carcinoma

Zeng

et al. 2006

J Histochem Cytochem.

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“…52,53 Here, we have shown that transfection of metastatic melanoma cells with Nterminal 146 aminoacids of ezrin, fused to GFP (ez-146) abrogated metastatic potential in vivo.…”

Section: Discussionmentioning

confidence: 99%

Pleiotropic function of ezrin in human metastatic melanomas

Federici

Brambilla

Lozupone

et al. 2009

Intl Journal of Cancer

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The membrane cytoskeleton cross-linker, ezrin, has recently been depicted as a key regulator in the progression and metastasis of several pediatric tumors. Less defined appears the role of ezrin in human adult tumors, especially melanoma. We therefore addressed ezrin involvement in the metastatic phenotype of human adult metastatic melanoma cells. Our results show that cells resected from melanoma metastatic lesions of patients, display marked metastatic spreading capacity in SCID mice organs. Stable transfection of human melanoma cells with an ezrin deletion mutant comprising only 146 N-terminal aminoacids led to the abolishment of metastatic dissemination. In vitro experiments revealed ezrin direct molecular interactions with molecules related to metastatic functions such as CD44, merlin and Lamp-1, consistent with its participation to the formation of phagocitic vacuoles, vesicular sorting and migration capacities of melanoma cells. Moreover, the ezrin fragment capable of binding to CD44 was shorter than that previously reported, and transfection with the ezrin deletion mutant abrogated plasma membrane Lamp-1 recruitment. This study highlights key involvement of ezrin in a complex machinery, which allows metastatic cancer cells to migrate, invade and survive in very unfavorable conditions. Our in vivo and in vitro data reveal that ezrin is the hub of the metastatic behavior also in human adult tumors. ' UICCKey words: CD44; merlin; Lamp-1; phagocytic vacuole; organelle acidity The molecular events governing progression from a primary tumor to an invasive, malignant tumor remain poorly defined despite intense scientific endeavor mostly due to molecular biology and biochemical data collected from non human models. 1 The metastatic phenomenon is characterized by a cascade of events that assumes the existence of very harmful cells within the primitive tumor mass. These cells must acquire the ability to breach underlying basement membrane, migrate through interstitial stroma, gain access to and migrate through blood or lymphatic vessels, attach, enter, survive and proliferate within metastatic organs.Mounting evidence suggesting that ezrin contributes to tumor metastasis promotion, arose mainly from experiments employing syngeneic implantation models correlated to gene expression profiling performed on pediatric tumors. 1,2 In human tumors, ezrin deregulation or impaired functionality is related to poor prognosis. [3][4][5][6][7][8][9] Ezrin belongs to the MERM family of cytoskeleton-associated proteins 10 and functions as a linker between the actin cortical cytoskeleton and various membrane-bound molecules 11,12 through its C-terminal and N-terminal domains, respectively.ERM proteins are implicated in a wide variety of important cellular processes. 10,13-18 Notably, ezrin is primarily involved in both cell-to-cell adhesion and cell adhesion to the ECM through association with ICAMs, CD44, E-cadherin and b-catenin. 12,19 To this family belongs also the tumor suppressor merlin (NF-2, schwannomin), whose loss is r...

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“…[17][18][19][20][21][22] For instance, the loss of ezrin expression in serous ovarian carcinomas was shown to be associated with poor survival. 34 Moreover, unlike osteosarcomas and adult high-grade sarcomas, ezrin overexpression was recently found not predictive of clinical outcomes in synovial sarcoma. 35 In our series, the high proportion and independent prognostic value of ezrin overexpression in GISTs suggest that this membrane/cytoskeleton anchor within the ERM protein family may represent a potential prognostic adjunct and/or therapeutic target and that those patients with ezrin-overexpressing GISTs should be closely monitored postoperatively.…”

Section: Discussionmentioning

confidence: 99%

Ezrin overexpression in gastrointestinal stromal tumors: an independent adverse prognosticator associated with the non-gastric location

Wei

et al. 2009

Modern Pathology

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Ezrin, a member of the ezrin-radixin-moesin family, acts as a link between the cell membrane and actin cytoskeleton to integrate cell adhesion-mediated signaling. It implicates tumor progression, metastatic dissemination, and adverse outcomes in several cancer types, including pediatric and adult sarcomas. Although ezrin upregulation was shown by cDNA expression profiling, no study has systematically evaluated the significance of ezrin expression in a large cohort of gastrointestinal stromal tumors (GISTs). Ezrin immunostaining was carried out on tissue microarrays of primary GISTs and assessable in 347 cases, 188 of which were successfully evaluated for mutation variants of KIT and PDGFRA receptor tyrosine kinase (RTK) genes by sequencing with or without screening by denatured high-performance liquid chromatography. These GISTs with known RTK genotypes were dichotomized into two prognostically different groups. The endogenous expression and phosphorylation of ezrin in GIST cell lines were analyzed by western blotting. By immunohistochemistry, ezrin overexpression was present in 66% of GISTs and significantly associated with the nongastric location (P ¼ 0.002) and decreased disease-free survival (P ¼ 0.032, univariately). However, it was not related to the National Institute of Health (NIH) risk category, Ki-67 labeling index, RTK genotypes, and other variables. In multivariate analyses, ezrin overexpression remained independently predictive of adverse outcome (P ¼ 0.008, risk ratio ¼ 2.363), together with Ki-67 labeling index 45% (Po0.001, risk ratio ¼ 3.581), high-risk category (Po0.001, risk ratio ¼ 2.156), and the non-gastric location (P ¼ 0.029, risk ratio ¼ 1.899). Despite the variation in the ezrin expression level, phosphorylated ezrin at threonine 567 was only detectable in GIST882 and GIST48 cells, but not in colonic smooth muscle cells. In conclusion, ezrin is frequently overexpressed in GISTs, especially those arising from the non-gastric sites. Given that its impact is independent of the NIH risk category, cell proliferation, and tumor location, ezrin immunoreactivity represents a valuable prognostic adjunct of GISTs, suggesting a causative role in conferring an aggressive phenotype.

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Ezrin immunoreactivity in relation to survival in serous ovarian carcinoma patients

Cited by 79 publications

References 20 publications

Altered Expression of Ezrin in Esophageal Squamous Cell Carcinoma

Altered Expression of Ezrin in Esophageal Squamous Cell Carcinoma

Pleiotropic function of ezrin in human metastatic melanomas

Ezrin overexpression in gastrointestinal stromal tumors: an independent adverse prognosticator associated with the non-gastric location

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