Positive Ezrin Expression Research Articles

Immunohistochemical negative expression of ezrin predicts poor prognosis in clear cell renal cell carcinoma

PurposeTo analyze the immunohistochemical expression of ezrin and moesin in clear cell renal cell carcinoma (ccRCC). These proteins, as part of the ezrin-radixin-moesin complex link the cell membrane to the actin cytoskeleton, affecting such processes as cell adhesion, cell survival, cell motility, and signal transduction. Our aim was to examine the impact of their expression on clinical outcomes and survival rates. Patients and methodsFive hundred seventy-five consecutive patients who had been treated surgically for ccRCC in a single center between 1985 and 2016 were selected. A single pathologist reviewed all cases to perform a uniform reclassification and determined the most representative tumor areas for construction of a tissue microarray. ResultsOf all ccRCC specimens, 106 (18.3%) were negative for ezrin, and 469 (81.7%) had positive ezrin expression; 16 (2.8%) were negative and 559 (97.2%) were positive for moesin, respectively. Ezrin expression was associated with pT stage (P < 0.001), clinical stage (P = 0.012), synchronic metastasis (P < 0.001), incidental tumors (P = 0.007), and International Society of Urological Pathology histological grade (P = 0.025). There was a correlation between moesin expression and clinical stage (P = 0.027), pT stage (P = 0.025), and pN stage (P = 0.007). Ezrin expression significantly influenced tumor-related deaths. By multivariate analysis, negative ezrin expression was an independent risk factor for disease-specific survival (HR 1.89; 95% CI 1.11–3.20). ConclusionsNegativity for ezrin in ccRCC patients significantly impacts survival rates. We encourage further prospective studies to analyze ezrin analysis to evaluate its significance in the prognosis of ccRCC.

The Prognostic Role of Ezrin and HER2/neu Expression in Osteosarcoma.

Osteosarcoma is the most common primary malignant bone tumor in Egypt. Ezrin is involved in cell adhesion to the extracellular matrix and in cell-cell interactions facilitating metastasis. HER2/neu is overexpressed in breast cancer and other types of cancer. This study aimed to assess the expression of ezrin and HER2/neu in 57 primary osteosarcoma cases and to correlate their expression with the available clinicopathologic parameters and the overall, metastasis-free and event-free survival. Both ezrin and HER2/neu were not expressed in the normal bone and they were upregulated in 82.5% and 71.9% of osteosarcoma, respectively. Positive ezrin expression was significantly associated with young age (below 25 y) (P=0.01), high grade (P=0.001), and short survival time (P=0.0001). Positive HER2/neu expression was significantly associated with high-grade osteosarcoma (P=0.04). Membranous HER2/neu expression was the only factor that showed significant impact on metastasis-free (P=0.002) and event-free survival (P=0.002). Ezrin was significantly correlated with HER2/neu expression (P=0.02). Advanced stage (P=0.0001), metastasis (P=0.0001), and recurrence (P=0.01) were the factors affecting the overall survival of osteosarcoma patients. Ezrin and HER2/neu are overexpressed and coexpressed in osteosarcoma with adverse prognostic features such as high grade. Membranous pattern of HER2/neu seems to be more important than the cytoplasmic pattern because of its impact on metastasis-free and event-free survival. Therefore, ezrin and HER2/neu could be potential prognostic markers and treatment targets for osteosarcoma.

Correlations of ezrin expression with pathological characteristics and prognosis of osteosarcoma: a meta-analysis.

We conducted a meta-analysis to comprehensively evaluate the correlations of ezrin expression with pathological characteristics and the prognosis of osteosarcoma. The MEDLINE (1966–2013), the Cochrane Library Database, EMBASE, CINAHL, Web of Science (1945–2013), and the Chinese Biomedical Database were searched without language restrictions. Meta-analyses conducted using STATA software were calculated. Ten studies met the inclusion criteria, including 459 patients with osteosarcoma. Meta-analysis results illustrated that ezrin expression may be closely associated with the recurrence of osteosarcoma or metastasis in osteosarcoma. Our findings also demonstrated that patients with grade III-IV osteosarcoma showed a higher frequency of ezrin expression than those with histological grade I-II osteosarcoma. Furthermore, we found that patients with positive expression of ezrin exhibited a shorter overall survival than those with negative ezrin expression. The results also indicated that positive ezrin expression was strongly correlated with poorer metastasis-free survival. Nevertheless, no significant relationships were observed between ezrin expression and clinical variables (age and gender). In the current meta-analysis, our results illustrated significant relationships of ezrin expression with pathological characteristics and prognosis of osteosarcoma. Thus, ezrin expression could be a promising marker in predicting the clinical outcome of patients with osteosarcoma.

High expression of ezrin predicts poor prognosis in uterine cervical cancer

BackgroundEzrin, a member of the ezrin/radixin/moesin (ERM) protein family, plays a pivotal role in tumor invasion and metastasis. This study is aimed to investigate the clinicopathological significance of upregulated ezrin protein expression in uterine cervical cancers.MethodsImmunohistochemical staining of ezrin protein was performed on uterine cervical cancer specimens from 235 patients. For comparison, 239 cases of cervical intraepithelial neoplasia (CIN), 17 cases of cervical glandular intraepithelial neoplasia (CGIN) and 52 normal cervix samples were also included. qRT-PCR was performed on fresh tissues to detect ezrin mRNA expression levels. HPV infection statuses were genotyped by oligonucleotide microarray, and 10-year survival rates were calculated using the Kaplan-Meier method for 109 cervical cancer patients.ResultsApical membranous distribution of ezrin protein was only observed in normal cervical glands, while perinuclear staining was only observed in cervical cancers. Strong cytoplasmic and diffuse localization of ezrin were frequently seen in the cervical cancers compared with the normal counterparts. Furthermore, this strongly positive ezrin expression was significantly higher in cervical cancers than in CIN, CGIN, and normal cervical epithelia. Ezrin overexpression was closely related with poor differentiation, late stage, and lymph node metastasis. Additionally, ezrin overexpression was associated with lower 10-year survival rate for patients with early stage cervical cancer, but not for patients with advanced stage.ConclusionsAberrant localization and overexpression of ezrin might be an independent effective biomarker for prognostic evaluation of cervical cancers.

Prognostic Value of Ezrin in Solid Tumors: A Meta-Analysis of the Literature

PurposeEzrin is a cytoskeletal protein involved in tumor growth and invasion. However its prognostic value for survival in patients with solid tumor remains controversial.MethodsSeveral databases were searched, including Pubmed, Embase and Cochrane databases. The endpoints were overall survival (OS), progression-free survival (PFS). The pooled hazard ratio (HR) or odds ratio (OR), and 95% confidence intervals (CI) were calculated employing fixed- or random-effects models depending on the heterogeneity of the included trials.ResultsTwenty-seven eligible trials involving 4693 patients were ultimately identified. A summary hazard ratio (HR) of all studies and sub-group hazard ratios were calculated. The combined HR suggested that a positive Ezrin expression had an impact on overall survival (OS) [1.95, 95% confidence interval (CI) 1.60–2.39; P<0.001] in all eligible studies and progress free survival (PFS): (2.30 95% CI 1.0–3.61; P = 0.001). Similar results were also observed in subgroup analysis, according to tumor types, regions, patients' number and publication year.ConclusionsOur findings suggested that Ezrin protein expression might be a factor for a poor prognosis in patients with solid tumor. So large well-designed prospective studies are now needed to confirm the clinical utility of Ezrin as an independent prognostic marker.

Expression and Functional Significance of Ezrin in Human Brain Astrocytoma

Ezrin is overexpressed in a variety of neoplastic cells and is involved in the later stages of tumor progression and metastasis. The present study investigated the expression and functional significance of ezrin in human brain astrocytoma. Ezrin expression was examined in specimens from healthy human brains (10 autopsies) or human astrocytoma (107 cases) by immunohistochemistry. All healthy specimens were negative for ezrin expression, while this expression was positive in a great majority of human astrocytoma tissues (96/107; 89.7%; p < 0.05 vs. healthy). Ezrin expression was positively correlated with tumor grade (r = 0.551, p < 0.01). Analysis of clinicopathologic data revealed that the post-operation disease-free survival times were significantly (p < 0.001) different between those with a strong positive ezrin expression and those with a weak or negative expression. Specifically, median DFS in patients with a strongly positive ezrin expression was 13 months (range 2-46 months), while it was significantly (p < 0.001) longer in patients with weakly positive or negative expression (median of 28 months, range 6-56 months). In conclusion, there is a strong association between ezrin expression and increased malignancy in astrocytoma. Thus, enhanced ezrin expression may play an important role in the development of astrocytoma. Our results further indicate that ezrin may be useful for grading of astrocytoma and as a molecular marker for the prognosis.

Ezrin expression and its phosphorylation in gastric carcinoma with lymphoid stroma and Epstein-Barr virus infection

Gastric carcinoma with lymphoid stroma (GCLS) is a unique variant of gastric carcinoma that represents prominent lymphocytic infiltration and is correlated with Epstein-Barr virus (EBV) infection. Ezrin expression and activation are crucial in tumor metastasis and induce cell migration of EBV-related nasopharyngeal carcinomas. Using immunohistochemical methods, the expression of total and phosphorylated ezrin (p-ezrin), Thr567, was examined in 104 GCLS cases, including 78 EBV-positive and 26 EBV-negative cases, as well as 29 non-GCLS cases. Positive ezrin expression was detected to be at markedly higher levels in GCLS compared to non-GCLS (P<0.0001). Furthermore, ezrin expression was detected to be at higher levels in EBV-positive compared to EBV-negative GCLS (P=0.0294). High expression of p-ezrin in GCLS was associated with positive lymph node metastasis (P=0.0187). In summary, these results demonstrated that ezrin overexpression is correlated with the histologic characteristics of GCLS and EBV infection. Phosphorylation of ezrin may, therefore, contribute to lymph node metastasis in GCLS.

Ezrin expression is associated with hepatocellular carcinoma possibly derived from progenitor cells and early recurrence after surgical resection

Heterogeneous biological characteristics of hepatocellular carcinoma may be attributed to the cellular origin of the tumor. Patients with hepatocellular carcinoma probably derived from hepatic progenitor cells had early tumor recurrence after surgical resection or liver transplantation, suggesting that these tumors have aggressive characteristics. Ezrin, a member of the ERM (ezrin-radixin-moesin) cytoskeleton-associated protein family, is highly expressed in several types of human cancers and correlations between its immunoreactivity and patient outcome have been shown. In this study, ezrin expression, as well as cytokeratin19 and cytokeratin 7 expression, which are regarded as progenitor cell/ductular markers were immunohistochemically assessed in cases of hepatocellular carcinoma. In normal livers, ezrin expression was not found in any cell types, whereas cytokeratin 7 and cytokeratin 19 were exclusively stained in bile duct cells. In contrast, in livers with chronic hepatitis or cirrhosis, positive ezrin expression was observed in ductular reactions with strong intensity and intermediate hepatobiliary cells with various intensity. Of 77 cases of hepatocellular carcinoma, 28 (36%) had positive ezrin expression, 32 (42%) had cytokeratin 7 expression, and 11 (14%) had cytokeratin 19 expression. Ezrin expression in hepatocellular carcinoma was significantly associated with cytokeratin 19 expression, but not with cytokeratin 7 expression. Patients with ezrin-positive hepatocellular carcinoma had a significantly higher prevalence of elevated serum α-fetoprotein. Patients with immunohistochemical ezrin-positive hepatocellular carcinoma demonstrated significantly shorter recurrence-free and overall survival compared to patients with ezrin-negative hepatocellular carcinoma. Multivariate analysis revealed positive ezrin expression and multiple tumors to be independently associated with early recurrence in patients with hepatocellular carcinoma after curative surgical resection. These results suggested that hepatocellular carcinoma with ezrin expression might be at least partly derived from hepatic progenitor cells. Measurement of ezrin expression might be used to identify patients with an increased risk of early recurrence.