Prognostic Value Of E-cadherin Research Articles

Role of E-cadherin and β-catenin in head and neck squamous cell carcinoma

Aim of the study: to present and summarize current data on the prognostic value of E-cadherin and β-catenin markers for head and neck squamous cell carcinoma, as well as to substantiate the potential benefit from implementing research results into clinical practice within the framework of a personalized approach to the treatment of head and neck squamous cell carcinoma.Material and Methods. We performed a literature search and review in Pubmed, Scopus, Google Scholar and RSCI databases regarding the association of the level of E-cadherin and β-catenin markers with disease prognosis, aggressiveness of tumor behavior and response to treatment.Results. Detailed information on the functions and mechanisms of E-cadherin and β-catenin proteins were presented and pathogenetic pathways involved in epithelial-mesenchymal transition were described. The results of studies on the association of β-catenin and E-cadherin expression levels with the prognosis of head and neck squamous cell carcinoma are collected and summarized. High expression levels of β-catenin and E-cadherin are associated with lymph node metastasis, poor prognosis and poor response to treatment.Conclusion. The expression levels of β-catenin and E-cadherin correlate with tumor invasion and lymph node metastasis, thus suggesting that β-catenin and E-cadherin can be used as potential markers of prognosis and treatment response in patients with head and neck squamous cell carcinoma. Further studies are needed to evaluate the co-expression of E-cadherin, β-catenin and other squamous cell carcinoma-associated markers, their impact on prognosis and treatment response, as well as their prognostic value.

Prognostic value of E-Cadherin and its tumor suppressor role in Saudi women with advanced epithelial ovarian cancer

ABSTRACT The extracellular matrix (ECM) disruption and cytoskeleton reorganization are crucial events in tumor proliferation and invasion. E-Cadherin (E-CAD) is a member of cell adhesion molecules involved in cell-cell junctions and ECM stability. The loss of E-CAD expression is associated with cancer progression and metastasis. This retrospective study aimed to assess E-CAD protein expression in ovarian cancer (OC) tissues and to evaluate its prognostic value. Patients and Methods: 143 formalin-fixed and paraffin-embedded (FFPE) blocks of primary advanced stages OC were retrieved and used to construct Tissue microarrays. Automated immunohistochemistry technique was performed to evaluate E-CAD protein expression patterns in OC. Results: E-CAD protein expression was significantly correlated with OC histological subtype (p < 0.0001), while borderline significant correlations were observed with both tumor grade (p = 0.06) and stage (p = 0.07). Interestingly, Kaplan-Meier survival analysis showed that OC patients with membranous E-CAD expression survived longer than those with no E-CAD expression mainly those at advanced stages (p < 0.009). Further in silico analysis confirms the key roles of E-CAD in OC molecular functions. Conclusion: we reported a prognosis value of membranous E-CAD in advanced stage OC patients. Further validation using larger cohorts is recommended to extract clinically relevant outcomes towards better OC management and individualized oncology.

The prognostic value of E-cadherin and Ki-67 compared to standard histopathologic examination in non-muscle invasive bladder cancer.

The objectives of this study were to determine the prognostic value of expression levels of selected biomarkers and their statistical analysis in relation to survival and standard histopathologic examination and other clinicopathologic variables in non-muscle invasive bladder cancer (NMIBC). Worldwide, bladder cancer is a frequent malignant disease with rising incidence. Characteristic invasiveness and high recurrence rates call for more diagnostic methods to obtain more accurate information. Prognosis is affected by a significant interpersonal variability of the disease. For this reason, constant search for alternative and better diagnostic methods is essential. We analysed cancer tissue from patients with Ta and T1 bladder cancer. E-cadherin and Ki-67 expression levels were analysed using immunohistochemical staining. The expression levels quantified to a percentual amount were statistically analysed in relation to survival and their frequency distribution in the study group. E-cadherin and Ki-67 expression levels show high association with tumor stage and grade (p<0.001), in contrast, the association with recurrence has proven insignificant. Patients with non-aberrant biomarker expression levels have much higher survival rates than the cases with aberrant expression. Low expression levels of Ki-67 and high expression levels of E-cadherin positively affect survival of patients, whereas aberrant expressions pose poorer prognosis (Tab. 2, Fig. 2, Ref. 33).

The Role of E-Cadherin as a Prognostic Biomarker in Head and Neck Squamous Carcinoma: A Systematic Review and Meta-Analysis.

In this study, we systematically investigated and analyzed articles focusing on the prognostic value of E-cadherin (E-cad) in human head and neck squamous cell carcinoma (HNSCC). Searching through the different databases, the studies examining the associations between E-cad and HNSCC prognosis were identified. Outcomes such as disease-specific survival and overall survival were considered acceptable. Hazard ratio (HR) with 95% confidence interval (CI) was used to demonstrate prognostic value. A total of 40 studies were systematically analyzed, and finally, 1939 subjects were included in our meta-analysis. Our findings showed that significant aberrant expression of E-cad was associated with poor survival. However, some studies showed increased expression of E-cad in metastatic lesions was associated with poor prognosis. Alteration in location of E-cad expression also showed significant association with cancer survival, i.e., increased cytoplasmic E-cad. We conducted a meta-analysis on the eligible articles using a random effect model because of moderate heterogeneity. Strong association between aberrant expression of E-cad and poor survival was demonstrated (pooled HR = 2.28; 95% CI 1.78-2.91). Aberrant expression of E-cad may be a promising prognostic signature for HNSCC, especially when it is used with other prognostic markers.

Prognostic Value of E-Cadherin and β-Catenin in Triple-Negative Breast Cancer.

To analyze the expression of E-cadherin and β-catenin in triple-negative breast cancer (TNBC) to assess their prognostic significance. The expression of E-cadherin and β-catenin was examined semiquantitatively and correlated with other pathologic factors and survival outcomes. Of 72 consecutive TNBCs, 56% showed reduced membranous expression of E-cadherin or β-catenin, with a strong correlation to each other. Of the clinicopathologic factors analyzed, tumor size and nodal status were significantly associated with overall survival and disease-specific survival, while the latter remained an independent factor by multivariate analysis. Reduced E-cadherin and β-catenin were both significantly associated with a poor overall survival and disease-specific survival by univariate and multivariate analyses. E-cadherin and β-catenin expression provides discriminative prognostic power independent of conventional pathologic factors, thus further reinforcing the important role of cell adhesion molecules in the process of tumor metastasis, especially in TNBC.

Expression and prognostic value of E-cadherin in laryngeal cancer

Conclusion: Down-regulation of ECD may associate with infiltrative tumor growth and result in poor prognosis. However, ECD expression is not significantly associated with tumor metastasis. Aim: To investigate the prognostic role of E-cadherin (ECD) expression in laryngeal cancer. Methods: In a clinical study, a total of 79 laryngeal cancer patients who received surgery were included in this study. The expression of ECD in laryngeal cancer tissue was detected by immumohistochemical staining. In an in vitro study, ECD up-regulated cells (Ad-ECD) and ECD down-regulated cells (sh-ECD) were cultured, along with interference by siRNA. Cell apoptosis was detected by flow cytometry. In an in vivo study, nude mice were injected with Ad-ECD, sh-ECD, and Hep-2 cells. The ECD expression and tumor metastasis in the brain, liver, and lung tissues were detected. Results: Clinical data showed that expression of ECD was statistically correlated with survival rate (p < 0.05), but not with other clinical characteristics, such as age, gender, lymphatic metastasis, and TNM staging. ECD was down-regulated in sh-ECD cells and the down-regulation significantly reduced apoptosis of Hep-2 cells. Tumor growth was significantly inhibited in the Ad-ECD group. Except the tumor tissue, no positive ECD expression or significant tumor cells were found in the brain, liver, and lung tissues.

Advantages of adjuvant chemotherapy for patients with triple-negative breast cancer at Stage II: usefulness of prognostic markers E-cadherin and Ki67

IntroductionTriple-negative breast cancer (TNBC), which is characterized by negativity for estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 (HER2), is a high risk breast cancer that lacks specific targets for treatment selection. Chemotherapy is, therefore, the primary systemic modality used in the treatment of this disease, but reliable parameters to predict the chemosensitivity of TNBC have not been clinically available.MethodsA total of 190 TNBC patients who had undergone a curative resection of a primary breast cancer were enrolled. The adjuvant chemotherapy was performed for 138 (73%) of 190 TNBC cases; 60 cases had an anthracyclin-based regimen and 78 a 5-fluorouracil-based regimen. The prognostic value of E-cadherin, Ki67 and p53 expression in the outcome of TNBC patients with adjuvant chemotherapy was evaluated by immunohistochemistry.ResultsThe adjuvant therapy group, especially those with Stage II TNBC, had a more favorable prognosis than the surgery only group (P = 0.0043), while there was no significant difference in prognosis between the anthracyclin-based regimen and 5-fluorouracil-based regimen. Patients with E-cadherin-negative and Ki67-positive expression showed significantly worse overall survival time than those with either E-cadherin-positive or Ki67-negative expression (P < 0.001). Multivariate analysis showed that the combination of E-cadherin-negative and Ki67-positive expression was strongly predictive of poor overall survival (P = 0.004) in TNBC patients receiving adjuvant chemotherapy. In contrast, p53 status was not a specific prognostic factor.ConclusionsAdjuvant therapy is beneficial for Stage II TNBC patients. The combination of E-cadherin and Ki67 status might be a useful prognostic marker indicating the need for adjuvant chemotherapy in Stage II TNBC patients.

Prognostic Significance of E-cadherin Expression and Peripheral Blood Micrometastasis in Gastric Carcinoma Patients

The primary objective is to evaluate the prognostic value of E-cadherin (E-cad) expression and peripheral blood micrometastasis (PBMM) in gastric carcinoma. Secondary objective is to study the association between these 2 markers and the clinicopathological features of the patients. This study took place at Ain Shams University Hospitals. A total of 30 patients with histologically proven gastric adenocarcinoma after curative surgical resection were enrolled in this study. E-cad expression was assessed in tumor tissue samples. Before the start of adjuvant chemoradiotherapy, fresh blood samples were collected to detect PBMM as indicated by cytokeratin18 mRNA expression using real-time quantitative polymerase chain reaction (RQ-PCR). Both abnormal E-cad expression and PBMM were significantly associated with lymph node metastasis, TNM stage, and lymphatic invasion. Moreover, PBMM was significantly associated with poor tissue differentiation and vascular invasion (P < .05). We found strong agreement between E-cad expression and presence of PBMM (P=.001). Both cases with altered E-cad expression and cases with positive PPMM showed shorter relapse-free survival (RFS) (P=.003 and <.001, respectively). Cox regression analysis showed that positive PBMM was independent predictor factor for relapse (hazard ratio [HR]=6.14; 95% confidence interval [95% CI]=1.06-35.63; P=.04). Cases with positive PBMM showed shorter overall survival (OS) (P=.001). In conclusion, loss of normal E-cad expression in gastric cancer showed a close correlation with the presence of PBMM. PBMM was associated with poor RFS independent of other clinicopathological features. Additionally, detection of PBMM was a significant indicator of OS, and intensive chemotherapy seems to be indicated for these patients.

Prognostic value of E-cadherin, CD34 in the patients with hepatocellular carcinoma

To study the expression of E-cadherin and CD34 in the tissues of hepatocellular carcinoma (HCC), to discuss the relationship between them and the clinical pathology and evaluate the prognosis of HCC patients. The expression of E-cadherin and CD34 in HCC tissues of 41 patients were examined by two-step methods of PV-6000 of immunohistochemistry. Clinical-pathological data, tumor recurrent rate and survival rate after hepatectomy were recorded and analyzed. The positive expression rate was observed in 48.78% for E-cadherin and 100% for CD34. The decreased E-cadherin expression were significantly associated with larger tumor, the high-dangerous group with invasion and poor differentiation of HCC tissues (chi(2) = 4.1881, 4.8118, 6.2695, P < 0.05). In the group with negative-expression of E-cadherin, the percent of tumor recurrence within 2 years after hepatectomy was higher and the rate of 5 years survival was significantly lower than the positive-expressed group. A significant negative-correlation between the expression of CD34 and the patients' age and the invasion of tumor (t = 1.9371, 1.9010, P < 0.05) were found. There was no relationship between the expression of E-cadherin and CD34 in HCC tissues. The patient with a negative-expression of E-cadherin in HCC tissues has a poor prognosis. No relationship between the expression of CD34 and tumor recurrence and patients' survival and no relationship between the expression of E-cadherin and CD34 was found.

Prognostic value of E-cadherin, beta-catenin, MMPs (7 and 9), and TIMPs (1 and 2) in patients with colorectal carcinoma

Therapy of colorectal tumors (CRC) based on histology and clinical factors is insufficient to predict the evolution of each patient. The finding of molecular abnormalities able to differentiate subgroups of patients with bad prognosis will improve our ability to treat them successfully. Our purpose was to analyze retrospectively the prognostic input of E-cadherin, beta-catenin, metalloproteinases (MMPs) (7 and 9), and tissue inhibitors of metalloproteinases (TIMPs) (1 and 2) in patients with a follow-up period of 5 years. Antigen expression was analyzed by immunohistochemistry. Prognostic evaluation was performed with the multivariate proportional hazards model. We demonstrated a concomitant loss of E-cadherin and beta-catenin at membranous level and an abnormal accumulation of nuclear beta-catenin. Besides, we found that all MMPs and TIMPs studied were overexpressed in CRC tissue. There was no association between the expression of any of these molecules and the known clinical-pathological parameters employed in CRC pathology. A multivariate analysis demonstrated that the overall survival could be independently predicted by the loss of E-cadherin and the overexpression of TIMP-2. The expression of E-cadherin and TIMP-2 could be relevant in determining the prognosis of CRC patients and providing a more accurate mechanism for their classification.

The Prognostic Value of E-Cadherin, α-, β-, and γ-Catenin in Urothelial Cancer of the Upper Urinary Tract

ObjectivesTo determine the value of loss of the expression of E-cadherin and cadherin-associated molecules as useful markers for both prognosis and bladder recurrence in patients with upper urinary tract cancer. Materials and methodsIn 61 paraffin-embedded nephroureterectomy specimens, the expression of E-cadherin and α-, β-, and γ-catenin was examined by immunohistochemical staining. To evaluate the prognostic significance, Kaplan-Meier survival curves were calculated and compared by the log-rank test. A multivariate test was performed to detect prognostic markers. ResultsNormal expression was found in 32 cases (52.5%) for E-cadherin, 41 cases (67.2%) for α-catenin, 42 cases (68.9%) for β-catenin, and 31 cases (50.8%) for γ-catenin. The expression patterns of E-cadherin and α-, β- and γ-catenin were significantly correlated with each other. Survival analysis showed a significant difference between normal and aberrant expression in each staining. Multivariate analysis revealed that tumor stage and the expression of E-cadherin were independent prognostic factors for cause-specific survival. In contrast, there was no significant correlation between the expression of E-cadherin and α-, β-, and γ-catenin and bladder recurrence. ConclusionOur data suggest E-cadherin may be a good prognostic marker for patients with upper urinary tract cancer.

E‐cadherin expression in invasive non‐lobular carcinoma of the breast and its prognostic significance

E-cadherin is a cell adhesion molecule that is expressed in normal breast tissue and is often considered useful as a phenotypic marker in breast cancer diagnosis, with absence of its expression frequently observed in tumours of lobular subtype. However, the clinicopathological and prognostic value of E-cadherin in the more frequent non-lobular types of breast carcinoma is unclear. E-cadherin expression was assessed immunohistochemically in a large and well-characterized series of invasive non-lobular breast carcinoma types (n=1665) with long-term clinical follow-up (median 56 months) using tissue microarray technology, to determine the relationship between its expression and primary tumour characteristics and disease outcome. Only membranous expression of E-cadherin was considered in this study and its expression was categorized as normal (H-score>100) or reduced [absent or below the median (score</=100)]. Complete absence of its expression (score=0) was detected in 7.2% of cases. On univariate analysis, reduced E-cadherin expression was associated with a reduced disease-free interval and overall survival and also with indicators of poor prognosis including larger tumour size, higher histological grade, development of distant metastasis and tumours negative for oestrogen receptors. No association between E-cadherin expression and lymph node status was found. On multivariate analysis, E-cadherin was an independent predictor of disease-free interval [hazards ratio (HR) 1.56, 95% confidence intrerval (CI) 1.23, 1.99; P<0.001] and overall survival (HR 1.53, 95% CI 1.09, 2.14; P=0.013) and there was some evidence that the prognostic value was greater in those with positive lymph nodes (P interaction=0.099). These results suggest that E-cadherin loss may play a role in progression, development of distant metastasis and recurrence in non-lobular invasive carcinomas of the breast and its assessment by immunohistochemistry may help in the identification of patients with poor outcomes.

Assay of E-cadherin by ELISA in Human Breast Cancers

E-cadherin is a membrane-bound adhesion glycoprotein. Loss of E-cadherin has been correlated with invasion and metastasis in model systems. Using a new ELISA, we found higher levels of E-cadherin in fibroadenomas than in primary breast cancers. Levels in primary cancers showed no significant relationship with either tumour size, nodal status or oestrogen receptor levels. Patients with breast cancers containing low levels of the adhesion protein had a significantly shorter disease-free interval than patients with high levels (P = 0.041). The prognostic value of E-cadherin, for disease-free interval, was also found in node-negative patients as well as in patients presenting with small tumors (⩽ 2 cm). In conclusion, loss of E-cadherin expression in human breast cancers is associated with increased metastatic potential as has previously been found in model systems. Loss of E-cadherin is thus likely to contribute to breast cancer progression.

Assay of E-cadherin by ELISA in human breast cancers

E-cadherin is a membrane-bound adhesion glycoprotein. Loss of E-cadherin has been correlated with invasion and metastasis in model systems. Using a new ELISA, we found higher levels of E-cadherin in fibroadenomas than in primary breast cancers. Levels in primary cancers showed no significant relationship with either tumour size, nodal status or oestrogen receptor levels. Patients with breast cancers containing low levels of the adhesion protein had a significantly shorter disease-free interval than patients with high levels ( P = 0.041). The prognostic value of E-cadherin, for disease-free interval, was also found in node-negative patients as well as in patients presenting with small tumors (⩽ 2 cm). In conclusion, loss of E-cadherin expression in human breast cancers is associated with increased metastatic potential as has previously been found in model systems. Loss of E-cadherin is thus likely to contribute to breast cancer progression.