Abnormal Expression Of E-cadherin Research Articles

Association between the expression of epithelial-mesenchymal transition (EMT)-related markers and oncologic outcomes of colorectal cancer.

Epithelial-mesenchymal transition (EMT) is a key step in the development of colorectal cancer (CRC) that confers metastatic capabilities to cancer cells. The present study aimed to assess the immunohistochemical (IHC) expression and impact of EMT markers, including E-cadherin, Vimentin, β-catenin, and SMAD4, on the oncologic outcomes of CRC. This was a retrospective review of 118 CRC patients. Tissue slides were retrieved from the slide archive and five tissue microarray construction blocks were constructed. IHC for E-cadherin, Vimentin, β-catenin, and SMAD4 was done. The main outcome was the association between abnormal marker expression and overall survival (OS), and disease-free survival (DFS). Adenocarcinomas accounted for 71.2% of tumors, whereas 25.4% and 3.4% were mucinous and signet ring cell carcinomas. The rates of lymphovascular invasion and perineural invasion were 72.9% and 20.3%, respectively. There was a positive, significant correlation, and association between the four markers. Abnormal expression of E-cadherin was associated with significantly lower OS (p < 0.0001) and similar DFS (p = 0.06). Abnormal Vimentin expression was associated with a significantly higher rate of distant metastasis (p = 0.005) and significantly lower OS and DFS (p < 0.0001). Abnormal expression of β-catenin was associated with significantly lower OS (p < 0.0001) and similar DFS (p = 0.15). Abnormal expression of SMAD4 was associated with significantly lower OS and DFS (p < 0.0001). Abnormal expression of all four markers was associated with a higher disease recurrence, lower OS, and lower DFS. Abnormal expression of each marker was associated with lower OS, whereas abnormal expression of Vimentin and SMAD4 only was associated with lower DFS.

Chronic Venous Disease in Pregnant Women Causes an Increase in ILK in the Placental Villi Associated with a Decrease in E-Cadherin.

Chronic venous disease (CVD) is a multifactorial vascular disorder frequently manifested in lower limbs in the form of varicose veins (VVs). Women are a vulnerable population for suffering from CVD, especially during pregnancy, when a plethora of changes occur in their cardiovascular system. Previous studies have indicated a worrisome association between CVD in pregnancy with the placental structure and function. Findings include an altered cellular behavior and extracellular matrix (ECM) composition. Integrin-linked kinase (ILK) is a critical molecule involved in multiple physiological and pathological conditions, and together with cadherins, is essential to mediate cell to ECM and cell to cell interplay, respectively. Thus, the aim of this study was to evaluate the implication of ILK and a set of cadherins (e-cadherin, cadherin-6 and cadherin-17) in placentas of women with CVD in order to unravel the possible pathophysiological role of these components. Gene expression (RT-qPCR) and protein expression (immunohistochemistry) studies were performed. Our results show a significant increase in the gene and protein expression of ILK, cadherin-6 and cadherin-17 and a decrease of e-cadherin in the placenta of women with CVD. Overall, this work shows that an abnormal expression of ILK, e-cadherin, cadherin-6 and cadherin-17 may be implicated in the pathological changes occurring in the placental tissue. Further studies should be conducted to determine the possible associations of these changes with maternal and fetal well-being.

Ras-association domain family 1 (RASSF1A) gene regulates progression, migration and invasion of bladder cancer

BackgroundBladder cancer is common malignant tumor around the world. Ras-association domain family 1 (RASSF1A) gene is inactivated in most of cancers. The aim of the study is to analyze the relationship between RASSF1A and the progression of bladder and investigate the effects of RASSF1A overexpression on bladder cancer cell in vitro. Materials and methodsImmunohistochemistry assay analyzed the RASSF1A expression in bladder tissue of bladder cancer patients. Besides, the data of 138 bladder cancer patients about RASSF1A expression was analyzed. Kaplan-Meier method analyzed the connection between disease free survival (DFS) and abnormal expression of RASSF1A and E-cadherin in bladder cancer patients. RASSF1A gene transfected the bladder cancer cells by lipofectamine. Cell proliferation was determined by methyl thiazolyl tetrazolium (MTT) assay. Cell apoptosis and cell cycle was detected using flow cytometry. Scratch assay evaluated cell migration, and transwell assay evaluated cell invasion. Western blot analyzed protein expression while qRT-PCR analyzed mRNA expression. ResultsBladder cancer tissues had lower RASSF1A expression compared with normal tissues, and the Patients with abnormal expression of RASSF1A had lower DFS and had higher possibility of recurrence and muscular layer infiltration. Besides, RASSF1A had significant difference with E-cadherin. RASSF1A overexpression inhibited the bladder cancer cell proliferation, migration and invasion, besides, it promoted apoptosis and the expression of E-cadherin and β-catenin. ConclusionRASSF1A may be a biomarker to evaluate the progression and recurrence of bladder cancer.

P0071 interacts with E-cadherin in the cytoplasm so as to promote the invasion and metastasis of non-small cell lung cancer.

As a member of the p120-catenin (p120ctn) subfamily, the p0071 study in tumor is very limited. We demonstrated the clinicopathological significance of p0071 in non-small cell lung cancer (NSCLC), as well as E-cadherin. Co-immunoprecipitation was used to detect the interaction of p0071 with E-cadherin in A549 and SPC cells (E-cadherin is mainly expressed in the cytoplasm of these cells). p0071 cytoplasmic expression was knocked down by siRNA in these cells and this effect on the RhoA activity and cell invasion and migration ability were measured. p0071 overexpression in the cytoplasm of tumor cell was correlated with lymphatic metastase and poor prognosis of NSCLC. The patients with both abnormal expression of p0071 and E-cadherin (cytoplasmic expression) had a statistically significant shorter survival than the patients without both abnormal expression (P < 0.05). There is a significant correlation between cytoplasmic overexpression of p0071 and E-cadherin in NSCLC tissues. p0071 interacted with E-cadherin in the cytoplasm of A549 and SPC cell lines. Treatment with siRNA-p0071 inhibited the invasion and migration ability of NSCLC cells. Above results confirmed that p0071 interacted with E-cadherin in the cytoplasm so as to promote the invasion and metastasis of NSCLC.

Expression of Pax2 and E-cadherin in renal cell carcinoma: correlation with clinicopathologic parameters

Objective To investigate the expression of paired box 2 (Pax2) and E-cadherin in human renal cell carcinoma (RCC) and their correlation with clinicopathologic parameters. Methods The RCC tissue microarrays containing 85 renal cell carcinoma specimens and 35 normal kidney tissue specimens were used to detect Pax2 and E-cadherin expressions by immunohistochemistry. Results The positive expression rate of Pax2 was 77.6% (66/85) in RCC specimens, which was significantly higher than that in 35 normal kidney tissue specimens (P 0.05). The expression of E-cadherin in RCC was significantly related to the size of tumor, histological classification, pathological grade and clinical stage (P<0.05). The positive expression rate of E-cadherin in survival group was significantly higher than that in death group (P<0.05). Conclusions The abnormal expressions of Pax2 and E-cadherin may play a crucial stage in development of human RCC. Detection of the expressions of Pax2 and E-cadherin can be used in the evaluation of malignant degree and prognosis of RCC. Key words: PAX2 transcription factor/ME; Cadherins/ME; Kidney neoplasms/ME

Expression and significance of serum E-cadherin in patients with papillary thyroid carcinoma

Objective:Experiments testing the concentration of serum E-cadherin were conducted through the patients with papillary thyroid carcinoma (PTC), nodular goiter and normal people. Combining the detection of E-cadherin protein in the tissues including papillary thyroid carcinoma,nodular goiter and normal thyroid tissues around adenoma,we analyze the effect and siginificance of E-cadherin in the papillary thyroid carcinoma.Method:The concentrations of E-cadherin in the serum of 86 cases of PTC patients, 16 cases of NG patients and 10 normal adults were detected by enzyme linked immunosorbent assay (ELISA) method, and the relationships between the serum level and clinical pathology characteristics of thyroid papillary carcinoma were explored. Western blot were used to detect the content of E-cadherin protein in tissues including PTC, nodular goiter tissues and normal thyroid tissues around adenoma.Result:The results showed that content of serum E-cadherin in PTC were significantly higher than those in nodular goiter tissues and normal thyroid issues (P< 0.05). There were no obviously differences between nodular goiter tissues and normal thyroid issues in the content of E-cadherin (P> 0.05). The content of E-cadherin protein in the tissues of PTC was evidently lower than those in nodular goiter tissues and normal thyroid tissues around adenoma (P< 0.05). There were no obviously differences between nodular goiter tissues and normal thyroid tissues around adenoma in the content of E-cadherin (P> 0.05). The abnormal expression of serum E-cadherin was correlated with the lymph node metastasis and pathological stage of PTC (P< 0.05). On the other hand,it is irrelevant to the gender､age and the tumor size of the patients (P> 0.05).Conclusion:The up-regulation of serum E-cadherin is correlated with the lymph node metastasis and pathological stage of PTC. The detection of the serum E-cadherin content plays a vital role in the aspects of early diagnosis and prognosis evaluation.

JNK signaling regulates E-cadherin junctions in germline cysts and determines primordial follicle formation in mice

Physiologically, the size of the primordial follicle pool determines the reproductive lifespan of female mammals, while its establishment largely depends on a process of germline cyst breakdown during the perinatal period. The mechanisms regulating this process are poorly understood. Here we demonstrate that c-Jun amino-terminal kinase (JNK) signaling is crucial for germline cyst breakdown and primordial follicle formation. JNK was specifically localized in oocytes and its activity increased as germline cyst breakdown progressed. Importantly, disruption of JNK signaling with a specific inhibitor (SP600125) or knockdown technology (Lenti-JNK-shRNAs) resulted in significantly suppressed cyst breakdown and primordial follicle formation in cultured mouse ovaries. Our results show that E-cadherin is intensely expressed in germline cysts, and that its decline is necessary for oocyte release from the cyst. However, inhibition of JNK signaling leads to aberrantly enhanced localization of E-cadherin at oocyte-oocyte contact sites. WNT4 expression is upregulated after SP600125 treatment. Additionally, similar to the effect of SP600125 treatment, WNT4 overexpression delays cyst breakdown and is accompanied by abnormal E-cadherin expression patterns. In conclusion, our results suggest that JNK signaling, which is inversely correlated with WNT4, plays an important role in perinatal germline cyst breakdown and primordial follicle formation by regulating E-cadherin junctions between oocytes in mouse ovaries.

食管鳞癌组织中nm23-H1和E-cadherin的表达及临床意义

目的：研究转移抑制基因(nm23-H1)和E-钙粘附蛋白(E-cadherin)在食管鳞癌组织中表达情况，了解两者之间的相关性及其与临床病理特征的关系。方法：采用免疫组化EnVision法检测60例食管鳞癌组织中nm23-H1和E-cadherin的表达情况，比较其相关性。结果：食管鳞癌组织中nm23-H1和E-cadherin的阳性表达率分别为38.3% (23/60)和41.7% (25/60)，正常食管黏膜组织中nm23-H1和E-cadherin的阳性表达均为90.0% (9/10)，nm23-H1和E-cadherin在食管鳞癌组织中的阳性表达率显著低于正常食管黏膜组织。nm23-H1、E-cadherin表达与食管癌患者的年龄、性别、组织类型无关(P > 0.05)，而与肿瘤分化程度、浸润深度、区域淋巴结转移及TNM分期有关(P O.05), but had correlation with degree of the differentiation, depth of tumor invasion, regional lymph node metastasis and TNM stage (P < 0.05). Nm23-H1 had positive correlation with E-cadherin. Conclusions: The expression of nm23-H1 and E-cadherin in esophageal squamous cell carcinomas was obviously lower than that in normal esophageal mucosa. The abnormal expression of nm23-H1 and E-cadherin are closely related to the degree of the differentiation of the cancer, depth of tumor invasion, lymph node metastasis and clinical stage; nm23-H1 and E-cadherin may be used as reference for assessing the malignancy and metastasis of esophageal squamous cell carcinomas.

JNK signaling regulates E-cadherin junctions in germline cysts and determines primordial follicle formation in mice.

Physiologically, the size of the primordial follicle pool determines the reproductive lifespan of female mammals, while its establishment largely depends on a process of germline cyst breakdown during the perinatal period. The mechanisms regulating this process are poorly understood. Here we demonstrate that c-Jun amino-terminal kinase (JNK) signaling is crucial for germline cyst breakdown and primordial follicle formation. JNK was specifically localized in oocytes and its activity increased as germline cyst breakdown progressed. Importantly, disruption of JNK signaling with a specific inhibitor (SP600125) or knockdown technology (Lenti-JNK-shRNAs) resulted in significantly suppressed cyst breakdown and primordial follicle formation in cultured mouse ovaries. Our results show that E-cadherin is intensely expressed in germline cysts, and that its decline is necessary for oocyte release from the cyst. However, inhibition of JNK signaling leads to aberrantly enhanced localization of E-cadherin at oocyte-oocyte contact sites. WNT4 expression is upregulated after SP600125 treatment. Additionally, similar to the effect of SP600125 treatment, WNT4 overexpression delays cyst breakdown and is accompanied by abnormal E-cadherin expression patterns. In conclusion, our results suggest that JNK signaling, which is inversely correlated with WNT4, plays an important role in perinatal germline cyst breakdown and primordial follicle formation by regulating E-cadherin junctions between oocytes in mouse ovaries.

Expression of E-cadherin in oral lichen planus.

Oral lichen planus (OLP) is a common lesion of the oral mucosa that can progress to cancer. E-cadherin is involved in intercellular adherence and the pathogenesis, development and metastasis of tumors, and is considered to be an important indicator of tumor progression and prognosis. The aim of this study was to investigate the expression of E-cadherin in OLP in order to elucidate its role in the pathogenesis and malignant transformation of OLP and provide evidence to support the early diagnosis and treatment of OLP with malignant potential. OLP specimens (n=52) and samples of normal oral mucosa (n=41) as the control were collected. Immunohistochemical staining was conducted to reveal the expression of E-cadherin in the OLP samples and normal oral mucosa. It was observed that 25 of the 52 OLP specimens exhibited normal positive expression of E-cadherin and 27 exhibited abnormal positive expression, corresponding to an abnormal positive rate of 51.92%. In the normal oral mucosa group, 39 of the 41 cases exhibited normal positive expression and 2 exhibited abnormal positive expression. The abnormal positive rate in the normal oral mucosa was 4.88%, which was significantly lower than that in the OLP group. The significantly elevated rate of abnormal positive expression of E-cadherin in the OLP group indicates the involvement of E-cadherin in the malignant transformation of OLP and supports the malignant potential of OLP.

E-cadherin, β-catenin, and α2β1 and α3β1 integrin expression in primary oral squamous cell carcinoma and its regional metastasis.

To investigate E-cadherin, β-catenin, and α2β1 and α3β1 integrins in 40 samples of non-metastatic and metastatic oral squamous cell carcinoma (OSCC) with positive cervical lymph nodes (LN). Immunohistochemistry was used to evaluate expression in the lesion center (LC) and invasive tumor front (ITF) of non-metastatic (n=18) and metastatic (n=22) OSCC and in the LN on the metastatic neoplastic cells (MNC; n=22). In metastatic OSCC, E-cadherin and β-catenin presented significantly lower cytoplasmic membrane expression in the ITF and MNC when compared to the LC and lower cytoplasmic expression in MNC when compared to the LC and ITF (p<0.05). Integrins α2β1 and α3β1 showed high cytoplasmic expression in the LC, ITF and MNC (p>0.05). A positive correlation was observed between E-cadherin cytoplasmic expression and α2β1 (p=0.860) and α3β1 (p=0.975) expression. When comparing the primary sites of metastatic and non-metastatic disease, β-catenin presented lower cytoplasmic membrane (p=0.013) expression in metastatic OSCC. E-cadherin presented low expression and the integrins high expression in both groups. Abnormal expression of β-catenin and E-cadherin associated with high expression of α2β1 and α3β1 integrins contribute to LN metastasis in OSCC.

Micropapillary pattern and poorly differentiated clusters represent the same biological phenomenon in colorectal cancer: a proposal for a change in terminology.

Colorectal carcinomas (CRCs) with a micropapillary pattern and those showing high counts of poorly differentiated clusters (PDCs) are characterized by a higher probability to develop nodal metastases and have a worse prognosis. In light of the morphologic similarity to the micropapillary component, we aimed to verify whether PDCs also display an inverted secretory pattern. The immunohistochemical expression of MUC1 and E-cadherin was assessed in a cohort of CRCs with PDCs and compared with that observed in CRCs without PDCs. PDCs in our cases always displayed an inverted MUC1 pattern. In addition, we found abnormal (lost or cytoplasmic) expression of E-cadherin in PDCs. The altered expression of MUC1 and E-cadherin may account for the aggressive behavior and higher metastatic potential of CRCs with high PDC counts and indicate an epithelial-mesenchymal transition. Our findings suggest that regardless of the morphologic aspect, PDCs and the micropapillary component may reflect the same biological phenomenon in CRCs. Thus, we wonder whether the micropapillary areas should be considered a variant of CRCs or more objectively counted as PDCs to predict prognosis. We also believe that the term PDC better describes the biological phenomena underlying this peculiar morphologic aspect in comparison with the misnomer micropapillary.

Expression of secreted frizzled related protein 1, β-catenin and E-cadherin in colorectal carcinoma and its clinicopathological significances

To investigate the expression of secreted frizzled-related protein 1 (SFRP1), β-catenin and E-cadherin in colorectal carcinoma and its clinicopathological significance. The expression of SFRP1, β-catenin and E-cadherin mRNA and protein in tumor and pericancerous tissue samples from 60 cases of colorectal cancer was assayed by reverse-transcription PCR and immunohistochemistry, respectively. The correlation of their expression with clinicopathological factors of colorectal cancer was analyzed. In 52/60 cases the relative mRNA expression of SFRP1 in cancer tissue and pericancerous tissue was 0.4837±0.1532 and 0.7170 ±0.1830; for β-catenin was 0.9293± 0.3705 and 0.6469±0.3166; and for E-cadherin was 0.5556±0.2535 and 0.9422±0.2372 (P<0.01), respectively. SFRP1 mRNA expression was associated with lymphatic metastasis (P<0.05). The positive rate of SFRP1 in colorectal cancer was 31.67% (19/60), and was significantly lower than that in pericancerous colorectal mucosa (75.00%, 45/60). No relationship between SFRP1 protein expression and clinical pathology was found. Abnormal expression rates of β-catenin and E-cadherin in colorectal cancer were 75.00% (45/60) and 58.33% (35/60), respectively, which were significantly higher than that in pericancerous colorectal mucosa (1.67% and 6.67%), respectively. Abnormal β-catenin and E-cadherin expression was associated with tumor differentiation, lymphatic metastasis and Duke's staging. SFRP1 protein expression was negatively correlated with β-catenin and E-cadherin expression (r=-0.517, -0.442, Ps<0.01). Down-regulation of SFRP1 in colorectal cancer may cause abnormal Wnt signaling and induce abnormal β-catenin and E-cadherin expression, indicating that SFRP1 might be involved in the development and progression of colorectal cancer, and could be a novel therapeutic target for colorectal cancer.

Abnormal expression of EMT-related proteins, S100A4, vimentin and E-cadherin, is correlated with clinicopathological features and prognosis in HCC.

We determined the expression of epithelial-mesenchymal transition (EMT) indicator proteins, E-cadherin (E-cad), vimentin (VIM), mucin 1 (MUC1) and S100 calcium-binding protein A4 (S100A4) in hepatocellular carcinoma (HCC) patient tissue samples. We also investigated the relationship between the expression of these proteins and clinicopathologic factors in HCC. Finally, we assessed the potential value of these markers as prognostic indicators of survival in HCC patients. The expression of E-cad, VIM, MUC1 and S100A4 EMT indicator proteins was assessed in tissue microarray HCC tissue sections and corresponding peritumoral normal tissues by immunohistochemistry. In addition, the expression for the four EMT indicator proteins was correlated with clinicopathological features of HCC and patient outcome. Comparison of clinicopathological characteristics and immunohistochemistry by χ(2) analysis revealed that downregulation of E-cad in HCC was significantly associated with later TNM cancer stage (P = 0.012), gross classification (P = 0.018), regional lymph node metastasis (P = 0.036) and liver cirrhosis (P = 0.028). Increased S100A4 expression in HCC was significantly associated with differentiation (P = 0.032), tumor with a complete fibrous capsule (P = 0.031) and portal vein invasion (P = 0.038). High VIM expression in HCC was significantly associated with high serum α-fetoprotein levels (P = 0.016). We also observed that low E-cad expression was significantly associated with overexpression of VIM (P = 0.001). Kaplan-Meier survival and Cox regression analysis revealed that low E-cad expression (HR = 0.164, 95 % CI 0.072 to 0.373, P < 0.001) and high serum α-fetoprotein levels (HR = 2.202, 95 % CI 1.054 to 4.598, P = 0.036) were independent prognostic factors in HCC. Our study demonstrates that high S100A4 and VIM expression and low E-cad expression correlate with an aggressive, malignant phenotype in HCC. These results also support a role for E-cad as a prognostic factor in HCC.

PRL-3 and E-cadherin show mutual interactions and participate in lymph node metastasis formation in gastric cancer

E-cadherin, a transmembrane adhesion molecule, and phosphatase of regenerating liver 3 (PRL-3) protein, a member of the family of tyrosine phosphatases, seem to be responsible for cancer cell migration. Therefore, the study objective was to determine a correlation between PRL-3 and E-cadherin, to assess their expression in neoplastic tissue and normal mucosa of the stomach, to analyze their effect on cancer advancement, and to evaluate their potential as prognostic markers in gastric cancer. The expressions of PRL-3 and E-cadherin were assessed immunohistochemically in 71 patients with gastric cancer. Positive expression of PRL-3 was observed in 42.2 % of gastric cancer cases, whereas E-cadherin expression was abnormal in 38 % of cases. The study revealed that the positive PRL-3 expression and abnormal E-cadherin expression were associated with mucinous gastric carcinoma and lymph node involvement. The former was also related to the infiltrating type of tumor and abnormal E-cadherin expression. The expression of PRL-3, but not of E-cadherin, was associated with shorter survival of patients. PRL-3 and E-cadherin exhibit interactions in gastric cancer and are involved in the formation of lymph node metastases. The PRL-3 protein can be an independent predictive factor of overall survival in gastric cancer patients.

English

Prostate cancer (PC) is the most common malignant tumor in men. Early identification of prostate cancer may result in improved cure rates and increased life expectancies. Gleason score and clinical range at the time of diagnosis are important factors to predict prognosis and outcome after therapy but additional accurate and reliable biomarkers are warranted. Few biomarkers of prostate cancer have been successfully implemented and used in clinical practice. In this study, we sought to determine the expression of E-cadherin, beta-catenin and human epidermal receptor (HER2) in biopsy specimens of prostate cancer with perineural invasion, and correlate them with Gleason score in order to verify the relationship between those markers and prostate cancer process. Our study demonstrated abnormal expression of E-cadherin, beta-catenin and HER2. On the other hand, our results showed no correlation between Gleason score and the expression of those markers in invasive prostate cancer tissues. Other different biomarkers remain to be identified, that potentially could improve the evaluation of prognostic of the patient. Key words: Biomarkers, biopsy specimens, Gleason score, perineural invasion, prostate cancer.

TFIIB-related factor 2 is associated with poor prognosis of nonsmall cell lung cancer patients through promoting tumor epithelial-mesenchymal transition.

In this study, we found that increased BRF2 protein expression was prevalent in NSCLC. Overexpression of BRF2 correlated with abnormal expression of E-cadherin, N-cadherin, and snail. Additionally, expression of BRF2 was found to be an independent prognostic factor in NSCLC patients. Furthermore, we showed that targeted knockdown of BRF2 expression could inhibit the migratory and invasive abilities of NSCLC cells and induced loss of the epithelial-mesenchymal transition of NSCLC cells. These results suggested that BRF2 overexpression in tumor tissues is significantly associated with the poor prognosis of NSCLC patients through promoting epithelial-mesenchymal transition (EMT) program.

Wnt/β-catenin pathway as a potential prognostic and predictive marker in patients with advanced ovarian cancer

Backgroundβ-catenin is the key protein in the WNT signalling pathway and it forms adherent junctions together with E-cadherin. In ovarian carcinoma, abnormal expression of β-catenin, E-cadherin and WNT-1 was observed, but their prognostic and predictive role is unclear. The aim of this study was to clarify the prognostic and predictive role of E-cadherin, β-catenin and WNT-1 in advanced epithelial ovarian carcinoma (AEOC).MethodsThe expression of E-cadherin, β-catenin and WNT-1 was determined by immunohistochemistry in AEOC. The correlation between expression of these proteins and progression-free survival (PFS) and overall survival (OS) was evaluated. Statistical analyses included Kaplan-Meier estimation, log-rank test, Spearman correlation and Cox proportional-hazards model.ResultsIn ovarian cancer, intense expression of E-cadherin, β-catenin and WNT-1 was found. In multivariate analysis, strong membrane β-catenin expression was an independent unfavourable predictor for PFS (HR 2.19, 95% CI 1.09-4.39; p = 0.028), while in univariate analysis, strong membrane β-catenin expression was a prognostic factor for OS in patients with AOC (p = 0.039). In multivariate analysis, only resistance to first-line chemotherapy was an adverse independent prognostic factor for OS (HR 16.84; 95% CI 5.07-55.98; p < 0.0001). Additionally, strong membranous β-catenin expression was associated with resistance to platinum-based chemotherapy (p = 0.027).ConclusionsThese findings support that WNT/β-catenin pathway and E-cadherin are important factors in advanced epithelial ovarian cancer.

Abnormal expression of serum soluble E-cadherin is correlated with clinicopathological features and prognosis of breast cancer.

BackgroundIncreased amounts of soluble E-cadherin (E-cad) have been found in the serum in various cancers, but the role of serum soluble E-cad in the prognosis of breast cancer patients has not been explored in Asian populations.Material/MethodBlood samples from 111 consecutive patients diagnosed with breast cancer and 55 healthy controls were investigated. Serum soluble E-cad expression levels were measured by enzyme-linked immunosorbent assay (ELISA) with an immunoassay kit according to the manufacturer’s directions. Kaplan-Meier analyses were used to evaluate the association between serum soluble E-cad expression level and survival. All statistical tests were 2-sided.ResultsThe serum levels of soluble E-cad in breast cancer patients were significantly higher than those of the control group (2218.9±319.6 ng/ml vs. 742.8±91.7 ng/ml, p<0.001). Serum levels of soluble E-cad correlated significantly with TNM stage (P=0.007), tumor grade (P=0.03), and lymph node metastasis (P<0.001). Kaplan-Meier analysis with the log-rank test indicated that high serum levels of soluble E-cad had a significant impact on overall survival (55.4% vs. 81.4%; P=0.032) and disease-free survival (36.8% vs. 67.8%; P=0.002) in breast cancer. Multivariate analysis revealed that serum levels of soluble E-cad were independently associated with overall survival and disease-free survival in breast cancer patients.ConclusionsSerum soluble E-cad level is an independent prognostic factor in Asian breast cancer patients.

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.