Expression of FRAT1 and β-catenin in human brain glioma and their significances

Objective: To investigate the expression of FRAT1 and β-catenin in human brain glioma, analyze the correlation between the expression and clinical pathological grades and the correlation of the two genes. Methods: FRAT1 and β-catenin were detected by immunohistochemistry in 84 human brain glioma tissues and 6 human normal brain tissues. Results: 66.7% (56/84) and 77.4% (65/84) of human brain glioma tissues expressed FRAT1 and β-catenin protein, whereas no FRAT1 and β-catenin protein expression was detected in human normal brain tissues. The expression levels of FRAT1 and β-catenin increased markedly with the ascending of pathologic grade of tumor specimens (r = 0.55, P < 0.01, r = 0.70, P < 0.01), there was a positive correlation between FRAT1 and β-catenin (r = 0.77, P < 0.01). Conclusion: FRAT1 and β-catenin over-expression maybe closely related with occurrence and development of human brain gliomas. The results provide important supplements for the research of Wnt/β-catenin pathway. Meanwhile, FRAT1 may act as a valuable biomarker for molecular diagnosis of glioma and a potential target for gene therapy of glioma.     

Alterations of E-cadherin and β-catenin in gastric cancer

Background  

The E-cadherin-catenin complex plays a crucial role in epithelial cell-cell adhesion and in the maintenance of tissue architecture. Perturbation in the expression or function of this complex results in loss of intercellular adhesion, with possible consequent cell transformation and tumour progression.     

Altered expression of β-catenin, E-cadherin, and E-cadherin promoter methylation in epithelial ovarian carcinoma

The aim of the study was to evaluate the immunoexpression of E-cadherin, β-catenin, and Ki-67, as well as the promoter methylation of E-cadherin gene in epithelial ovarian cancer (EOC), as well as to find a possible relationship between the immunoexpression and hypermethylation. Promoter methylation was studied using methylation-specific PCR in 86 malignant cases, 14 low malignant potential (LMP) tumors and 19 benign cystadenomas. Immunohistochemical expression was carried out in 64 malignant cases, 8 LMP tumors, and 11 benign cystadenomas. Immunoexpression of E-cadherin was reduced in EOC, while 100 % expression was seen in LMP tumors and benign cystadenomas. An interesting observation was the nuclear expression of E-cadherin in a high percentage of cancers, which showed a positive correlation with Ki-67. Β-Catenin expression showed heterogeneous localization with increased nuclear localization, which was significantly higher in cases that did not express E-cadherin. Promoter methylation of E-cadherin was 36, 14, and 11 % in EOC, LMP tumors, and benign cystadenomas, respectively. Our results suggest that reduced expression of E-cadherin is associated with promoter methylation of E-cadherin gene, in addition to providing evidence for the aberrant nuclear localization of E-cadherin in EOC.     

Prognostic significance of Wnt-1, β-catenin and E-cadherin expression in advanced colorectal carcinoma

Wnt/β-catenin pathway plays an important role in initiation and progression of colorectal oncogenesis. The aim of this study was to determine expression and localization of E-cadherin, β-catenin and Wnt-1 proteins in colorectal tumors. Expression of β-catenin, E-cadherin and Wnt-1 was determined by immunohistochemistry on advanced colorectal cancers. Abnormal expression of E-cadherin, β-catenin, Wnt-1 was observed. Additionally, we revealed correlations between levels of studied proteins and histoclinical data. In multivariate analysis nuclear β-catenin, higher carcinoembryonic antigen serum level before treatment, female sex and tumor localized in colon or rectum were independent unfavorable prognostic factors. These findings support the hypothesis that Wnt/β-catenin pathway plays an important role in advanced colorectal carcinoma.     

乳腺癌组织中E-cadherin、β-catenin及cyclin D1表达的相关性研究

背景与目的上皮性钙粘素(E-cadherin)通过连接素(catenins)与细胞骨架相连介导细胞同质粘附反应,β-catenin除与E-cadherin结合介导细胞粘附反应外,还作为Wnt信号转导通路的重要成分与肿瘤发生密切相关。本研究通过检测乳腺癌组织中E-cadherin、β-catenin及cyclinD1的表达,探讨E-cadherin、β-catenin在乳腺癌发生、发展中的意义。方法采用免疫组织化学SP法检测60例乳腺癌组织中E-cadherin、β-catenin、cyclinD1的表达。结果乳腺癌组织中有29例(48.3%)E-cadherin、18例(30.0%)β-catenin正常表达,28例(46.7%)cyclinD1过度表达。E-cadherin正常表达病例中,31.0%(9/29)的病例呈现cyclinD1过度表达,而E-cadherin异常表达病例中,61.3%(19/31)的病例呈现cyclinD1过度表达,E-cadherin异常表达与cyclinD1的过度表达有显著的正相关性(rs=0.303,P<0.05)。有42例癌组织表现出β-catenin的异常表达,其中57.1%(24/42)的病例出现cyclinD1的过度表达,而β-catenin正常膜表达病例中,22.2%(4/18)的病例呈现cyclinD1的过度表达。β-catenin的异常表达与cyclinD1的过度表达有显著的正相关性(rs=0.321,P<0.05)。结论E-cadherin和β-catenin的异常表达可能通过促使或激活cyclinD1的过度表达导致乳腺癌的发生和发展。     

Osteopontin,E-cadherin,and β-catenin expression as prognostic biomarkers in patients with radically resected gastric cancer

A correlation between osteopontin, E-cadherin, β-catenin, and cyclooxygenase 2 overexpression and poor clinicopathological features and prognosis has been previously suggested in gastric cancer. This translational study was aimed at assessing the correlation of these immunohistochemical biomarkers with outcome in patients with radically resected gastric cancer. We analyzed osteopontin, E-cadherin, β-catenin, and cyclooxygenase 2 expression by immunohistochemistry in 346 primary gastric tumor tissue samples from patients enrolled in the ITACA-S trial. This phase III study randomized patients with radically resected gastric cancer to receive adjuvant chemotherapy with either 5-fluorouracil and leucovorin or a sequential regimen of infusional 5-fluorouracil and leucovorin plus irinotecan followed by cisplatin and docetaxel. High expression of osteopontin was correlated with high histological grade, diffuse histotype, and peritoneal relapse, but not with TNM stage. Moreover, osteopontin overexpression was associated with higher risk of tumor recurrence and metastases, and was an independent prognostic factor for both relapse-free and overall survival of gastric cancer patients following adjuvant chemotherapy. Abnormal E-cadherin expression and abnormal β-catenin expression were correlated with more advanced disease stage, and as a consequence, with poor outcome. Our results suggest that osteopontin overexpression is a valuable independent predictor of tumor recurrence and survival in patients with radically resected gastric cancer.     

Expression of APC, β-catenin and E-cadherin in Tunisian patients with gastric adenocarcinoma: clinical significance

Aberrant activation of the Wnt signalling pathway is a key feature of many cancers. β-Catenin, adenomatous polyposis coli (APC) and E-cadherin are major players in this pathway. The aim of this study is to examine the expression of β-catenin, APC and E-cadherin in tumour tissues of 80 Tunisian patients with gastric carcinoma and to determine the methylation status of the APC promoter in tumour tissues. Associations between protein expression and clinico-pathological parameters, including prognosis, were performed. Positive expression of β-catenin, APC and E-cadherin was observed in 77.5, 68.7 and 60 % of cases, respectively. Tumours lacking membranous expression of β-catenin had greater extent of lymph node metastasis, poor differentiation and advanced T-stage. The expression of E-cadherin correlated with poor differentiation (P?=?0.05) and β-catenin expression (P?=?0.004). With regards to prognosis, the overall survival time was significantly prolonged for patients showing normal β-catenin expression (exclusively or predominantly membranous staining) alone or combined with positive APC expression (P log rank?=?0.008 and 0.003, respectively). The methylated pattern of APC promoter 1A was detected in 43.8 % of cases and correlated with T-stage (P?=?0.046) and distant metastasis (P?=?0.037). No correlation was found between the methylated profile of APC promoter 1A and the expression of APC protein in tumour tissues. Our findings suggest that deregulation of the Wnt pathway via abnormal expression of β-catenin and E-cadherin occurred frequently in gastric carcinoma and correlated with worse clinical behaviour.     

The expressions and significance of α-, β-catenins and cyclin D1 in breast cancers

Objective  To study the relationship between expressions of α-, β-catenins and cyclin D1 and the occurrence, infiltration and metastasis of breast cancer. Methods  High sensitive S-P immunohistochemical method was used to detect the protein expressions of α-, β-catenins and cyclin D1 in the 60 cases of breast cancer tissues. Results  Abnormal immunoreactivities of α-and β-catenins were observed in 37 (61.7%) and 42 (70%) cases of breast cancer tissues, respectively. There were 28 cases (46.7%) who showed cyclin D1 overexpression. The abnormal expression rates of α-and β-catenins in infiltrating lobular carcinoma (ILC) were significantly higher than those in infiltrating ductal carcinoma (IDC) (P < 0.05), but they had no relations to the extent of differentiation and lymphatic metastasis of breast cancer (P > 0.05). The overexpression rate of cyclin D1 was correlated with tumor stage and lymphatic metastasis of breast cancer (P < 0.05), but not with histological type and the extent of differentiation (P > 0.05). Cyclin D1 overexpression was observed in 57.1% (24/42) of these cases that showed abnormal staining of β-catenin, but only observed in 22.2% (4/18) of these cases with normal membranous staining of β-catenin. There was a significantly positive correlation between the abnormal expression of β-catenin and overexpression of cyclin D1 (r _s = 0.321, P < 0.05). Conclusion  The abnormal expression of β-catenin may play an important role in the genesis of breast cancer by triggering cyclin D1 overexpression in breast cancer. The abnormal expressions of α-and β-catenins are not a key factor in malignant cell metastasis in breast cancer, but may also involve in the progress.     

Expression of TGF-β1, Snail, E-cadherin and N-cadherin in Gastric Cancer and Its Significance

OBJECTIVE To investigate the expression of TGF-β1,Snail,E-cad-herin and N-cadherin in gastric cancer(GC),and to examine its relationship to malignant features of the tumors. METHODS The expression of TGF-β1,Snail,E-cadherin and N-cadherin proteins was detected in GC and adjacent tissues by immunohistochemical staining,and compared with the clinico-pathological data. RESULTS Positive rates of expression for TGF-β1,Snail,E-cadherin and N-cadherin were 63.5%,83.3%,37.5%and 44.8%in GC,and 28.8%, 41.3%,100%,11.3%in adjacent tissues,respectively.The expression of all four proteins showed a significant difference between the GCs and adjacent tissues(P<0.05).The positive rate of TGF-β1,Snail and N-cadherin,or the negative rate of E-cadherin expression was significantly related to the differentiated degree,histological type,invasion and metastasis of GC.In addition,the expression of N-cadherin was positively related to that of TGF-β1, but negatively related to that of E-cadherin.There was negative correlation between expression of E-cadherin and TGF-β1 and Snail in GC(P<0.05). CONCLUSION The over-expression of TGF-β1 and Snail and decreased expression of E-cadherin and the abnormal expression of N-cad-herin were involved in the process of invasion and metastasis of GC.The data showed that E-cadherin might switch to N-cadherin.TGF-β1 and Snail might play a fundamental role in the process.     

Expression of E-cadherin, β-catenin and topoisomerase IIα in leiomyosarcomas

Introduction  

The expression of E-cadherin, β-catenin and topoisomerase II has been associated with clinical outcome of several cancers including sarcomas. We aimed to evaluate the expression of these markers in leiomyosarcomas (LMS).     

应用组织芯片检测食管鳞状细胞癌中APC、β-catenin、E-cadherin与cyclinD1的表达及其意义

背景与目的：食管鳞状细胞癌（esophageal squamous cell carcinoma,ESCC）的发生是个多因素多阶段的演进过程。Wnt信号转导通路在肿瘤发生发展中起重要作用。本研究探讨4种Wnt通路上的蛋白在食管鳞癌发生中的作用及在早期诊断中的意义。方法：制作由199例食管鳞癌组织与其癌旁164例正常粘膜、34例基底细胞增生和30例不典型增生上皮组成的组织芯片,应用免疫组化方法检测APC、 β-catenin、E-cadherin、cyclin D1的表达情况。结果：APC和E-cadherin在ESCC阳性率分别是69．6％、19．6％,均低于各自正常组（98．0％、96．3％,均为P〈0．01）, β-catenin和cyclin D1在ESCC的异常表达率分别是65．5％和70．9％,均高于各自正常组（1．2％,0．8％,均为P〈0．01）。按正常粘膜→基底细胞增生→不典型增生→ESCC的顺序,APC低表达发生在ESCC, β-catenin和E-cadherin表达异常始于不典型增生．cyclinD1过表达始于基底细胞增生。随着ESCC分化程度由高到低的改变,APC、E．cadherin和cyclinD1阳性率逐渐减少, β-catenin逐渐增加。 β-catenin的表达与APC无相关（r=-0．10,P〉0．05）,与E．cadherin呈负相关（r=-0．31,P〈0．01）,与cyclinD1呈正相关（r=0．49,P〈0．01）。结论：APC、E-cadherin、 β-catenin和cyclinD1可能在ESCC发生过程中起重要作用。 β-catenin、E-Cadherin和cyclinD1的表达检测有助于ESCC的早期诊断。     

Expression and clinical significance of E-cadherin, β-catenin and E-cadherin-catenins complex in breast cancer and precancerous lesions简

Objective： The aim of our study was to observe the expressions and clinical Significance of E-cadherin, β-catenin and E-cadherin-catenins complex in breast cancer and precancerous lesions, and analyze the relationship between the expressions and clinicopathological features in breast cancer. Methods： Immunhistochemical UltraSensitiveTM S-P method was employed to detect the expression of E-cadherin, β-catenin and E-cadherin-catenins complex in 128 cases of invasive ductal carcinomas, 89 cases of ductal carcinoma in situ and 57 cases of atypical ductal hyperplasia, 53 cases of usual ductal hyperplasia breast tissues were selected as a control group. The express of E-cadherin, β-catenin and their relationship with mult biological parameters including histological grade, region lymph node metastasis, distant metastasis and recurrence on files were also assessed. Results： （1） The staining patterns character of E-cadherin, β-catenin and E-cadherin-catenins complex： In UDH breast tissues, E-cadherin and a-catenin were expressed on cell membrane of ductal and acinic cells, showing cellular contour and border among cells. The abnormal expression of the three proteins occurred in breast invasive ductal carcinomas, ductal carcinoma in situ and atypical ductal hyperplasia tissues, showing cytoplasmic or nuclear staining, decrease and loss of cytomembrane staining. （2） The abnormal expression rates of E-cadherin, β-catenin and E-cadherin-catenins complex in invasive ductal carcinomas were 53.91%, 65.63% and 81.25%, which were significantly higher than that in ductal carcinoma in situ, atypical ductal hyperplasia, usual ductal hyperplasia tissues （P 〈 0.01）. Compared with usual ductal hyperplasia breast tissues group, the abnormal expression rates of E-cadherin, β-catenin and E-cadherin-catenins complex were significantly decreased （P 〈 0.01） in the breast cancer group. However, there was no significance of the abnormal expression rate between ductal carcinoma in situ and atypical ductal hyperplasia tissues groups （X2 = 0.76, P = 0.38; x2 = 0.14, P = 0.70; x2 = 0.81, P = 0.37; X2 = 2.19, P = 0.14） （P 〉 0.05）. （3） There was a significantly difference in the mean E-cadherin, β-catenin and E- cadherin-catenins complex frequency between estrogen receptor ＆ progesterone receptor positive IDC group and negative group, epidermal growth factor receptor type 2 （HER2/neu） positive and negative groups, Ki-67 proliferation index 〈 14% and 〉 14% groups, histological grade （I ＋ II） and grade III invasive ductal carcinomas groups, with lymph node metastasis, distant metastasis and recurrence groups （P 〈 0.05） and without groups （P 〈 0.05）. However, there was no difference in the mean E-cadherin, β-catenin and E-cadherin-catenins complex frequency between age （_〈 50 years vs 〉 50 years）, tumor diameter （〈 2 cm vs 〉 2 cm） （P 〉 0.05）. Conclusion： In breast cancer, the expressions of E-cadherin, β-catenin and E-cadherin-catenins complex are abnormally decreased and are correlated with pathology grade, differentiation disturbance and metastasis. E- cadherin and β-catenin may be as the predictors for prognosis. Combined detection may improve accuracy and sensitivity of predicting metastasis and prognosis of breast Cancer.     

Prognostic value of β-catenin,c-myc,and cyclin D1 expressions in patients with esophageal squamous cell carcinoma

Esophageal squamous cell carcinoma (ESCC) is one of the most frequently diagnosed malignant tumors in North China. We have identified that Wnt2/β-catenin pathway is activated in ESCC cells and sodium nitroprusside (SNP) and siRNA against β-catenin not only inhibit the expressions of β-catenin and its major downstream effectors including c-myc and cyclin D1 but induce cell cycle arrest and apoptosis. The purpose of the present study was to analyze the relationship between pathological parameters including invasion depth and lymph node metastasis and the expressions of β-catenin, c-myc, and cyclin D1 in order to evaluate their values of prognosis in patients with ESCC. The expressions of β-catenin, c-myc, and cyclin D1 were detected immunohistochemically in the resected cancer tissues from 40 patients with ESCC. The β-catenin expression was reduced in 22 (55.0%) patients, which was closely correlated with invasion depth (P = 0.023) and lymph node metastasis (P = 0.003). There was the positive c-myc expression in 21 (52.5%), which was significantly correlated with invasion depth (P = 0.009) and lymph node metastasis (P = 0.001). Furthermore, the results of survival rates analyzed by Kaplan–Meier curve revealed that patients with the reduced expression of β-catenin had a poorer prognosis than those with the preserved expression (P = 0.031), and patients with the positive expression of c-myc also had a significantly poorer prognosis than those with the negative expression (P = 0.008). These findings demonstrate that β-catenin pathway plays a crucial role in the progression of ESCC, suggesting that both β-catenin and c-myc may be used as markers for predicting the prognosis of patients with ESCC.     

Role of β-catenin in cisplatin resistance,relapse and prognosis of head and neck squamous cell carcinoma

Background

Head and neck squamous cell carcinoma (HNSCC) is one of the most common types of cancer in India with high incidence and rapid recurrence rates. Here, we aimed to investigate the role of β-catenin, a developmental pathway gene, in HNSCC therapy resistance, DNA damage response, recurrence and prognosis.

Methods

In total 80 HNSCC samples were included. Western blot, immunohistochemistry and qRT-PCR analyses were performed to assess β-catenin expression in the cut margin and tumor areas of each sample. Kaplan-Meier analyses were performed to correlate β-catenin expression with the survival and prognosis of HNSCC patients. In addition, chemo-resistance, DNA damage response and DNA repair capacities were evaluated in HNSCC-derived cell lines through LiCl-mediated up-regulation and siRNA-mediated silencing of β-catenin expression.

Results

We observed β-catenin up-regulation in cut margin areas of recurrent patients compared to their corresponding tumor regions, which subsequently could be associated with poor prognosis. In addition, we found that LiCl-mediated up-regulation of β-catenin in HNSCC-derived cells led to cisplatin resistance, evasion of apoptosis, enhanced DNA repair and enhanced migration. The effects of β-catenin silencing correlated with its putative role in chemo-resistance and DNA damage response.

Conclusion

From our results we conclude that β-catenin may contribute to HNSCC therapy resistance and disease relapse. As such, β-catenin may be explored as a therapeutic target along with conventional therapeutics.