OBJECTIVE: To evaluate the correlation of the expression of E-cadherin, alpha-catenin, beta-catenin and the clinicopathological features in endometrial cancer (EC) and atypical complex endometrial hyperplasia (ACEH). METHODS: Immunohistochemical (IHC) staining of E-cadherin, alpha-catenin, beta-catenin was performed in tissues of 6 ACEHs, 44 endometrioid ECs. We analyzed the correlation of the expression of IHC staining with the prognostic factors according to tumor stage of ACEH and EC, histopathologic grade, and myometrial invasion. RESULTS: According to tumor stage, reduced E-cadherin expression and abnormal alpha-catenin expression were observed more frequently in advanced stage (reduced E-cadherin: ACEH 0%, stage I-II 47.2%, stage III-IV 62.5%, p=0.050; abnormal alpha-catenin: ACEH 0%, stage I-II 27.8%, stage III-IV 62.5%, p=0.035). All of the IHC staining showed no correlation with the depth of myometrial invasion but showed correlation with presence of myometrial invasion (reduced E-cadherin: invasion(-) 14.3%, invasion(+) 66.7%, p =0.001; abnormal alpha-catenin: invasion(-) 7.1%, invasion (+) 46.0%, p=0.010; abnormal beta-catenin: invasion(-) 7.1%, invasion(+) 63.0%, p=0.000). According to histological differentiation only abnormal beta-catenin expression shows relationship with histopathologic grade (grade 1:23.1%, grade 2:60%, grade 3:62.5%, p=0.039). CONCLUSION: Expression of E-cadherin and alpha-catenin showed significantly more reduced expression in EC than in ACEH, and more reduced expression in advanced stage, myometrial invasion and high histopathologic grade. And alpha-catenin showed more frequent abnormal expression in advanced stage, myometrial invasion and beta-catenin showed more frequent in myometrial invasion, high histopathologic grade significantly. These results suggests that the expression of E-cadherin and alpha-catenin, beta-catenin in EC and ACEH could be related to prognosis of the tumor.
alpha Catenin ; beta Catenin ; Cadherins* ; Endometrial Hyperplasia* ; Endometrial Neoplasms* ; Female ; Prognosis

The E-cadherin, alpha-catenin, and beta-catenin expressions were immunohistochemically investigated in paraffin-embedded materials of 80 cases of colorectal adenocarcinomas. The staining similar to normal colorectal mucosa with preserved strong membranous staining pattern was considered normal or preserved expression. The X2 test was used to analyse the statistical correlation of cadherin/catenin expression with clinicopathologic parameters and the Breslow test for the correlation with survival length. Normal colorectal mucosa showed strong membranous expression of cadherin/catenin complex. The reduced E-cadherin, alpha-catenin, and beta-catenin expression were found in 53/80 (66.3%), 46/80 (57.5%), and 44/80 (55.5%) cases of colorectal cancers examined, respectively. There were significant correlations between E- cadherin and alpha -catenin (p=0.035), and between alpha-catenin and beta-catenin (p=0.013). The reduced E-cadherin expression was associated with histologic dedifferentiation, tumor depth, lymph node metastasis, clinical stage (p<0.05), poor clinical outcome in stage II (p=0.016) and the reduced alpha-catenin expression with lymph node metastasis and clinical stage (p<0.05). Reduced expression of two or more proteins was correlated with lymph node matastasis, histologic dedifferentiation, clinical stage, and survival (p<0.05). The present study demonstrates a significant down-regulation of E-cadherin and alpha-catenin expression in colorectal cancer is associated with tumor invasiveness, histologic dedifferentiation, lymph node metastasis, and clinical stage. These results suggest that E-cadherin and alpha-catenin may be useful markers of invasiveness, lymph node metastatic potential, and clinical stage and of value as prognostic markers in the earlier stage. Further studies are needed to confirm the prognostic value of these cadherin/catenin complex.
Adenocarcinoma* ; alpha Catenin* ; beta Catenin* ; Cadherins* ; Colorectal Neoplasms ; Down-Regulation ; Lymph Nodes ; Mucous Membrane ; Neoplasm Metastasis

PURPOSE: E-cadherin is an adhesion molecule essential for tight connection between cells, forming the cadherin/catenin complex. Truncated beta-catenin disrupts the interaction between E-cadherin and alpha-catenin, leading to the loss of intercellular adhesion. Met protein, the hepatocyte growth factor receptor, plays important roles in signal transduction. We investigated the relationships between the expressions of E-cadherin, beta-catenin, and c-met protein and the clinicopathological and prognostic parameters in gastric adenocarcinomas. MATENRIALS AND METHODS: The patterns of E-cadherin, beta- catenin, and c-met protein expression were studied using immunohistochemistry in formalin-fixed, paraffin-embedded archival tissues from 76 surgically resected gastric adenocarcinomas. RESULTS: Increased expressions of E-cadherin, beta-catenin, and c-met were more significantly correlated in early gastric cancers (EGC) than in advanced gastric cancers (AGC) (P=0.002, P=0.003 and P=0.026). The positive immunoreactivities of all three markers were markedly lower in signet ring-cell type and poorly differentiated type lesions than in intestinal-type lesions. Decreased expression of the beta-catenin protein correlated well with increased tumor invasion depth (P=0.039), and increased lymph node metastasis correlated well with reduced expression of c-met (P=0.046). CONCLUSION: In gastric cancers, reduced expressions of the E-cadherin, beta-catenin, and c-met proteins may play some role in poorer tumor differentiation, deeper tumor invasion, and increased lymph node metastasis. Also, the c-met gene is thought to play a specific role in the mechanism of the yet unknown catenin action.
Adenocarcinoma* ; alpha Catenin ; beta Catenin* ; Cadherins* ; Immunohistochemistry ; Lymph Nodes ; Neoplasm Metastasis ; Proto-Oncogene Proteins c-met ; Signal Transduction ; Stomach Neoplasms

PURPOSE: E-cadherin plays a crucial role in cell-cell adhesion in epithelial tissues. The function of E-cadherin is thought to be regulated by its associated cytoplasmic proteins including alpha-catenin. Recent studies have shown a correlation between decreased E-cadherin and alpha-catenin expression and tumor invasion and metastasis. METHODS: We conducted an immunohistochemical staining of epithelial (E)-cadherin and alpha-catenin expression in 129 tissue samples taken from colorectal cancer patients undergoing surgical treatment by the avidin-biotin-peroxidase complex method. We classified tumors into three types according to the expression modality. Cancer cells with strong expression at the cell-cell boundaries were defined as two positive (++);, when the expression was positive, but not concentrated at the cell-cell boundaries and weak, they were defined as one positive (+);, and when the tumor showed no staining, they were defined as negative (-). The relationships between these three expression types and the clinicopathological features of colorectal cancer were investigated. RESULTS: The expression type of E-cadherin and alpha-catenin was two positive (++) in 5 and 20 of the cancer tissue specimens, one positive (+) in 66 and 56, and negative (-) in 58 (45%) and 53 (41.1%). Negative expression of E-cadherin and alpha-catenin were significantly correlated with tumor differentiation, Dukes'stage, and lymph node metastasis of the colorectal cancer patients (P<0.05). CONCLUSION: The expression type of E-cadherin is signifi-cantly corretated to that of alpha-catenin, and the loss of their expression indicates the invasion and metastasis of colorectal cancer. To predict tumor invasion and metastasis in colorectal carcinoma, it is useful to investigate both the expression of E-cadherin and of alpha-catenin.
alpha Catenin* ; Cadherins* ; Colorectal Neoplasms* ; Cytoplasm ; Humans ; Immunohistochemistry ; Lymph Nodes ; Neoplasm Metastasis

The study was aimed to investigate the synergistically effect of interferon-&alpha; (IFN-&alpha;) and homoharringtonine (HHT) on the proliferation, apoptosis, cell cycle of K562 cells and the expression of β-catenin. The proliferation, apoptosis, cell cycle and β-catenin mRNA expression of K562 cells treated with IFN-&alpha; and/or HHT were assayed with MTT, flow cytometry or RT-PCR respectively. The results showed that HHT alone, but not IFN-&alpha; alone, displayed a proliferation inhibition, apoptosis induction, G(0)/G(1) phase block and down-regulation of β-catenin expression in K562 cells with concentration- and time-dependent manners. The expression level of β-catenin mRNA after being treated with HHT was 0.5576 ± 0.0373, which were lower than that in control group (0.9369 ± 0.0142). The down-regulation of β-catenin expression in group of IFN-&alpha; combined with HHT was higher significantly than that in HHT group (0.3737 ± 0.0529 vs 0.5576 ± 0.0373, P < 0.05). Otherwise, HHT combined with IFN-&alpha; did not demonstrate obvious toxicologic effect on bone marrow mononuclear cells. It is concluded that IFN-&alpha; combined with HHT can enhance the cytotoxic effect of HHT on K562 cells, which may be associated with down-regulation of β-catenin expression.
Cell Proliferation ; drug effects ; Harringtonines ; pharmacology ; Humans ; Interferon-alpha ; pharmacology ; K562 Cells ; beta Catenin ; genetics ; metabolism

N,N-Diethylnitrosamine (DEN) has been proved to have carcinogenic potential in the initiation or promotion stage and the transformed cells proliferate to form preneoplastic nodules which are positive for placental form of glutathione S-transferase (GST-P). E-Cadherin, a member of the cadherin family, is expressed in epithelial cells. To evaluate the role of adhesion molecules (E-Cadherin, alpha-catenin, and beta-catenin), which have not been well understood in carcinogenesis, we investigated the changes of E-cadherin, alpha-Catenin and beta-Catenins by immunohistochemistry and immunoblotting in DEN-induced hepatocarcinogenesis of rat liver. In addition, the sequential analysis of histopathology and the expression of GST-P were also examined. Immunoreactive areas for GST-P were gradually increased from early period of carcinogenesis and strong GST-P positive foci were noted in various lesions, especially in the clear cell and eosinophilic cell nodules. Immunohistochemically, the E-Cadherin expression was increased in DEN-treated preneoplastic nodules in 4 and 10 weeks and hepatocellular carcinomas displayed relatively reduced expression compared with the hyperplastic nodules. But alpha- and beta-catenin expression was increased in hyperplastic nodules and hepatocellular carcinomas. Immunoblotting studies revealed that the level of alpha-catenin (cytosol and membranous fraction) was overexpressed in hyperplastic nodules as well as hepatocellular carcinomas, which showed markedly increased expression. The membranous fraction of beta-catenin was markedly increased in 10 weeks of DEN treatment and slightly reduced in hepatocellular carcinomas. These findings suggest that during DEN-induced hepatocarcinogenesis, the clear cell and eosinophilic cell nodules expressing GST-P in their cytoplasm are early transformed cell nodules. The altered expression of E-Cadherin and catenins is closely related with tumor propagation. Loss or reduced expression of E-cadherin may play a role in the progression of late hyperplastic nodule to hepatocellular carcinoma in DEN-induced rat hepato carcinogenesis.
alpha Catenin ; Animals ; beta Catenin ; Cadherins* ; Carcinogenesis ; Carcinoma, Hepatocellular ; Catenins* ; Cytoplasm ; Eosinophils ; Epithelial Cells ; Glutathione Transferase* ; Glutathione* ; Humans ; Immunoblotting ; Immunohistochemistry ; Liver* ; Rats*

OBJECTIVETo explore the relationship between the E-cadherin catenin complex and invasiveness of pituitary adenoma.

METHODSThe expression of E-cadherin catenin complex was determined by immunohistochemistry in 78 cases of human pituitary adenomas including invasive adenoma 44 cases, noninvasive adenoma 34 cases and the relativity of their expressions with hormone-producing, pituitary apoplexy and necrosis or cystoid change, tumor diameter were analyzed.

RESULTSThe invasive group had a significantly lower expression of E-cad and alpha-cat than that of noninvasive group (chi-squared = 13.969, P < 0.01). There was no statistical significance for beta-cat expression between the invasive group and noninvasive group (chi-squared = 0.430, P > 0.05). Moreover, the expressions of beta-cad and alpha-cat were significantly lower in macro-adenoma group than that in micro-adenoma group (chi-squared = 5.038, P < 0.05). The expression of E-cad was significantly lower in endocrine inactive group than that in endocrine active group (chi-squared = 4.614, P < 0.05). The expression of beta-cat was significantly lower in the group with apoplexy and necrosis than that in the group without apoplexy and necrosis (chi-squared = 6.701, P < 0.05).

CONCLUSIONSThe reduction of E-cad catenin complex is related to invasiveness and clinical pathological characteristics.

Adolescent ; Adult ; Aged ; Cadherins ; metabolism ; Female ; Humans ; Male ; Middle Aged ; Neoplasm Invasiveness ; Pituitary Neoplasms ; metabolism ; pathology ; Young Adult ; alpha Catenin ; metabolism ; beta Catenin ; metabolism

BACKGROUND AND OBJECTIVES: E-cadherin and catenins (alpha, beta, gamma, p120cat) are important epithelial adhesion molecules in normal epithelial cells. Loss of E-cadherin-catenin adhesion is an important step in the progression of epithelial cancers such as tongue cancer. E-cadherin and catenins expression in carcinoma of human tongue was evaluated in relation to their clinicopathological features and prognostic values. SUBJECTS AND METHOD: Thirty-nine specimens of tongue squamous cell carcinoma were examined in this study. These patients were all treated by primary surgery without prior radiotherapy or chemotherapy. The specimens of formalin-fixed and paraffin-embedded tumor tissues were investigated by immunohistochemical analysis using E-cadherin and catenin (alpha, beta, gamma, p120cat) monoclonal antibodies. RESULTS: The expressions of E-cadherin, alpha-catenin, beta-catenin, gamma-catenin and p120cat in cell membranes were reduced or absent in 71.8%, 74.4%, 76.9%, 59.0% and 82.1% of the tumors examined, respectively. The reduced expressions of alpha-catenin and gamma-catenin in the cell membranes was cor-related with tumore differentiation (p=0.018, p=0.004, respectively). There were significant correlations between E-cadherin and expressions of the four cantenins in the cell membranes of tongue cancer. There were no correlations between beta-catenin and p120cat expression in the cytoplasm, cell nucleus and clinicopathological features. There was significant correlation between E-cadherin expression and Kaplan-Meier survival curves. CONCLUSION: These results suggest that E-cadherin and catenins (alpha, beta, gamma, p120cat) can be used as prognostic markers of human tongue squamous cell carninoma. The result of beta-catenin and p120cat absence in the nucleus suggests that Wnt/Wingless signaling or Kaiso transcription did not occur in the human tongue squamous cell carcinoma.
alpha Catenin ; Antibodies, Monoclonal ; beta Catenin ; Cadherins* ; Carcinoma, Squamous Cell ; Catenins ; Cell Membrane ; Cell Nucleus ; Cytoplasm ; Drug Therapy ; Epithelial Cells ; gamma Catenin ; Humans ; Kaplan-Meier Estimate ; Prognosis ; Radiotherapy ; Tongue Neoplasms* ; Tongue*

PURPOSE: Among the cell adhesion molecules, alpha-catenin and E-cadherin play an important part in maintaining normal cell structure. The change in expression of cell adhesion molecules affects the invasion and metastasis of a tumor and the prognosis for patients. In this study, we evaluated the relationship between the expression of cell adhesion molecules and the histopathologic characteristics of stage III colon cancer. METHODS: The relationship between the immunohistochemical expression of cell adhesion molecules and tumor progression were statistically analyzed in 40 patients with stage III colon cancer. RESULTS: There were no statistically significant correlations between loss of membranous alpha-catenin and E-cadherin expressions and such variables as histologic differentiation and lymph node disease based on the criteria of the American Joint Committee on Cancer (AJCC). A significant correlation, however, existed between depth of mural invasion and loss of expressions of both alpha-catenin and E-cadherin (P=0.001 and P=0.002, respectively). Expressions of both alpha-catenin and E-cadherin were also significantly decreased in patients showing liver metastases during follow-up (P=0.019 and P=0.015, respectively). CONCLUSION: Immunohistochemical analyses of alpha-catenin and E-cadherin expressions may be available as predictors for distant metastasis, especially in stage III colon cancer. Such analyses may also help to identify appropriate therapeutic strategies and the need for intensive follow-up in patients with stage III colon cancer.
alpha Catenin ; Cadherins ; Cell Adhesion Molecules ; Colon ; Colonic Neoplasms ; Follow-Up Studies ; Humans ; Joints ; Liver ; Lymph Nodes ; Neoplasm Metastasis ; Prognosis

OBJECTIVES: To observe the clinical efficacy of moxibustion as an adjunctive treatment for rheumatoid arthritis (RA) based on conventional medication and its effects on serum sclerostin (SOST) and β-catenin levels, exploring the potential mechanisms by which moxibustion may protect joint bones in RA patients. METHODS: Seventy-six RA patients were randomly divided into an observation group (38 cases, 3 cases dropped out) and a control group (38 cases, 4 cases were eliminated, 2 cases dropped out). The patients in the control group were treated with conventional oral medication; based on the treatment of the control group, the patients in the observation group were treated with moxibustion. The direct moxibustion was applied at Zusanli (ST 36) on both sides and ashi points around small joints, and indirect moxibustion was applied at Shenshu (BL 23) on both sides and ashi points around large joints. The treatment was given three times a week for a total of 5 weeks. The count of pain and swollen joint, morning stiffness score, disease activity score of 28 joints (DAS28), visual analogue scale (VAS) score, health assessment questionnaire (HAQ) score, and serum levels of SOST, β-catenin, and tumor necrosis factor-α (TNF-α) were evaluated before and after treatment in the two groups. RESULTS: Compared those before treatment, after treatment, both groups showed a reduction in pain and swollen joint count (P<0.01, P<0.05), morning stiffness, DAS28, VAS, and HAQ scores (P<0.01, P<0.05), with the observation group having lower scores than the control group (P<0.01). Serum levels of SOST, β-catenin, and TNF-α after treatment in the observation group were lower than those in both before treatment and the control group (P<0.01, P<0.05). There was a positive correlation between the difference in serum β-catenin levels before and after treatment and the difference in serum SOST (r=0.578, P<0.001) and TNF-α (r=0.403, P<0.05) levels in the observation group. CONCLUSIONS In addition to medication, moxibustion as an adjunctive treatment could significantly alleviate joint pain and reduce disease activity in RA patients, suggesting a potential role in joint protection. This mechanism may be related to the inhibition of the inflammatory factor TNF-α, regulation of β-catenin levels, and reduction in the production of the endogenous negative regulator protein SOST within the Wnt/β-catenin signaling pathway.
Humans ; Moxibustion ; Tumor Necrosis Factor-alpha ; beta Catenin ; Acupuncture Points ; Arthritis, Rheumatoid/therapy* ; Arthralgia ; Adaptor Proteins, Signal Transducing