E-cadherin In Patients Research Articles

Expression of Ki-67 and E-cadherin in patients with non-small cell lung cancer attending a tertiary care hospital

Background: E-cadherin and Ki-67 expressions may provide real-time insights into the tumor's status and can be utilized as targeted therapeutics for lung cancer. We aimed to explore the expression of Ki-67 and E-cadherin in non-small cell lung cancer (NSCLC) patients and to identify their association with clinicopathological features. Methods: In this cross-sectional study, forty formalin-fixed paraffin-embedded (FFPE) NSCLC tissue blocks were identified from January to October 2022, based on hospital records from the Department of Pathology of National Institute of Diseases of the Chest and Hospital, Dhaka Medical College and Hospital. Samples were reevaluated for tissue quality, diagnosis, and exclusion-inclusion criteria. Finally, twenty-five samples were analyzed, and relevant clinicopathological data were collected from patients or authorized representatives. Ki-67 and E-cadherin expression were analyzed by immunohistochemistry and their relationships with each other. Results: Ki-67 expression was positive in 40% of the NSCLC tissue, and E-cadherin was negative in 40% of the NSCLC tissue. No statistically significant relation was found between the expressions of Ki-67 and E-cadherin. No statistically significant association was found in Ki-67 and E-cadherin expressions with clinicopathological characteristics except E-cadherin with comorbidity. Conclusion: Positive expression of Ki-67 and negative expression of E-cadherin was found in two-fifths of NSCLC tissues but not significant. Simultaneous estimated of Ki-67 and E-cadherin may contribute to the treatment planning and predict prognosis of the NSCLC patients.

Neoadjuvant chemotherapy reduces the levels of HMGB1 and E-cadherin in patients with breast cancer

This study investigated the changes in serum tumor marker levels in patients with breast cancer (BC) after neoadjuvant chemotherapy (NACT) and their potential as prognostic factors in NACT. A total of 134 consecutive patients with BC treated at our hospital between January 2019 and December 2021 were retrospectively analyzed. Patients were treated with NACT based on the docetaxel, epirubicin, and cyclophosphamide (TEC) regimen and assessed for marker levels, T cell subsets, and therapeutic outcomes. Receiver operating characteristic (ROC) curves were constructed to evaluate the predictive performance of the markers. Outcome assessments showed that NACT effectively reduced the tumor size, leading to increased complete remission, partial remission, stable disease, and significantly reduced disease progression. Improved immune function has also been observed after NACT. The levels of two (E-cadherin and HMGB1) out of five markers (CA153, CK19, CEA, E-cadherin, and HMGB1) were significantly reduced after NACT before surgery compared with those at admission, suggesting that NACT modulates the levels of biomarkers. ROC analysis revealed that the area under the curve (AUC) of HMGB1 and E-cadherin combination was 0.87 for discrimination of therapeutic response with a sensitivity and specificity of 91.3% and 88.4%, respectively. Serum tumor marker levels were reduced after NACT in patients with BC. The reduction was most prominent for HMGB1, followed by E-cadherin. These biomarkers can be used to predict the therapeutic response to NACT with an AUC of 0.87, thus offering a new tool to monitor treatment progress in NACT for patients with BC.

Salivary and serum levels of soluble E-cadherin in patients with gastrointestinal cancers: A comparative study.

According to the literature, high levels of salivary soluble E-cadherin may be lined to advanced stage and poor prognosis in cancers. This research aimed at comparing salivary and serum levels of soluble E-cadherin in cases with esophageal, gastric, and colorectal cancers. This case-control research was performed on 68 patients with gastrointestinal cancers and 57 healthy volunteers as a control group to measure salivary and serum levels of soluble E-cadherin using ELISA kits. The results showed a statistically significant difference between salivary and serum levels of soluble E-cadherin in the case group, as opposed to the control group (P = 0.031). The salivary level of soluble E-cadherin in the control group was 2.138 ng/mL on average lower than that that in the case group. The median salivary level of soluble E-cadherin among cases with lymph node involvement was significantly higher compared with its median level in the control group (P = 0.049). Soluble E-cadherin salivary level and other variables, such as metastasis and cancer stage, were directly correlated, but it was not statistically significant. According to the findings, the salivary level of soluble E-cadherin among cases with gastric cancer could be considered as a prognostic marker, but the diagnostic value of saliva could not be judged in esophageal and colorectal cancers because of small sample size, and more investigations are required for a definite conclusion.

Serum soluble E-cadherin is a new potential marker for assessing the severity of gout.

Currently, millions of people suffer from gout-related disorders, which cause a great economic and health burden worldwide. However, so far, there is no effective serum marker to evaluate the severity of gout. Over the years, more and more experimental data have demonstrated that soluble E-cadherin (sE-cadherin) may act as a pivotal regulator involving in the initiation and development of various types of diseases. Unfortunately, the precise role of sE-cadherin in gout-related complications remains to be investigated. In this work, we try to investigate the potential function of E-cadherin in patients with gout-related disorders. Serum sE-cadherin levels and other clinical parameters, from 37 patients with hyperuricaemia, 107 patients diagnosed with gout, 76 gout arthritis patients and 125 healthy adults were analysed in this study. Here, we firstly show that sE-cadherin levels are significantly elevated in gout patients and gout are patients compared to those in healthy subjects, and that there is no significant difference between patients with hyperuricaemia and control group. Next, to further our understanding of how sE-cadherin acts as a new marker for assessing the severity of gout-related diseases, we nd that serum sE-cadherin values are signi cantly positively correlated with the serum in ammatory markers, including hsCRP and IL-1β in patients with gout and gout are. We also present evidence that serum sE-cadherin values are associated with oxidative stress in patients with gout-related complications. This is perhaps best illustrated by the observation that serum sE-cadherin values are significantly correlated with oxidative markers including SOD and soluble NOX2. Taken together, our ndings strongly support the idea that serum sE-cadherin levels may be a new candidate biomarker for evaluating and stratifying the severity of gout-related complications.

A preliminary study on the association between epithelial-mesenchymal transition and circulating tumor cells in renal cell carcinoma.

BackgroundCirculating tumor cells (CTCs) are considered useful prognostic factors for various cancers, and in 2014, our research group conducted a comparative experiment of CTC detection in patients with renal cell cancer (RCC). However, the reason for the low detection rate of CTCs in cancer patients using the CellSearch® system is still unknown, although it has been hypothesized to be attributed to the likelihood that CTCs undergoing epithelial-mesenchymal transition (EMT) do not express the CTC biomarkers cytokeratin (CK)8/18/19 or epithelial cell adhesion molecule (EpCAM). The overall aim of the current study was to investigate the expression levels of CK8/18/19 and EpCAM in relation to the EMT biomarkers vimentin and E-cadherin in patients with RCC.MethodsPatients with RCC who had undergone radical nephrectomy or partial resection between May 2014 and December 2014 were initially recruited.ResultsAmong 34 RCC patients, nine co-expressed EpCAM and CK8/18/19 in primary tumor tissues. The CellSearch® results showed that CK8/18/19 was expressed in 5 of 6 patients (5/6) and EpCAM was expressed in 6 patients (6/6). However, the isolation by size of tumor cells (ISET) technique showed these were co-expressed in only four of the 10. The expression of CK8/18/19, EpCAM, vimentin, and E-cadherin was distributed unequally in different enumeration groups of CTCs (all P>0.05), and the positive expression of CK8/18/19 was correlated with neutrophil number and tumor size (P<0.05). The positive expression of vimentin was correlated with the Karnofsky Performance Status (KPS) score and clinical stage of renal cancer patients (P<0.05).ConclusionsOur results indirectly proved the occurrence of EMT in the formation of CTCs by comparing and analyzing the expression of CK8/18/19 and EpCAM in renal cancer tissues and the detection results of CTCs.

Shikonin contributes to intestinal epithelial cell differentiation through PKM2/NRF2-mediated Polyol pathway

BackgroundAlteration of polyol pathway is a critical event in serials of disease, including inflammatory bowel disease (IBD). Shikonin, an inhibitor of PKM2, has been reported to exert a wide range of biological and pharmacological properties. However, the function of shikonin-mediated polyol pathway in IBD remained to be addressed. MethodsWe conducted WB and qPCR to analyze the effect of shikonin on intestinal epithelial cell differentiation. IF, IP, luciferase assay and ChIP were employed to demonstrate the mechanism that shikonin regulated cell differentiation through polyol pathway. Elisa was used to measure the serum sorbitol in subjects enrolled in this study, and the clinical sample was collected to detect PKM2, AR and NRF2 expression. ResultsHerein, we showed that shikonin treatment in HT-29 and CaCO2 cells not only contributed to CDX2 and its targets expression, including MUC2 and villin, leading to cell differentiation, but also induced NRF2-mediated AKR1B1 and AKR1B10 expression, resulting in increasing AR activity. A synergistic effect on CDX2-mediated cell differentiation was observed in CaCO2 cells in response to cotreatment with shikonin and AR agonist bortezomib for 24 hours, while aldose reductase inhibitor fidarestat treatment in CaCO2 cells reversed the enhanced CDX2 expression caused by shikonin. Mechanistically, PKM2 interacted with NRF2, and this interaction was enhanced in response to shikonin stimulation, resulting in NRF2 phosphorylation and nuclear translocation, which further increased AKR1B1 and AKR1B10 transactivation. Moreover, both AKR1B1 and AKR1B10 expression were decreased, while PKM2 was increased in intestinal epithelial cells labeled with E-cadherin in patients with IBD, and a negative clinical relationship was observed between PKM2 and AKR1B1/AKR1B10, respectively. What's more, the serum sorbitol level was decreased in patients with IBD. ConclusionThese results suggested that shikonin could promote intestinal cell differentiation through NRF2-mediated polyol pathway, implying that shikonin may be a promising therapeutic drug for the treatment of IBD.

E-Cadherin Expression in Patient with Gastric Carcinoma in Relation to Histological Prognostic Parameters

Background: E-cadherin (epithelial-cadherin), encoded by the CDH1 gene, is a transmembrane glycoprotein playing a crucialrole in maintaining cell-cell adhesion. E-cadherin has been reported to be a tumor suppressor and to be down regulated ingastric cancer. Objective: The aim of this study is to find out the expression of E-cadherin in patients with gastric carcinoma and it's relation tohistological prognostic parameters. This study also aimed to investigate the morphological parameters of prognostic value:histologic type and tumor grading, depth of invasion, lympho-vascular invasion, perineural invasion and lymph node metastasis. Methods: This descriptive cross sectional study was carried out from March, 2015 to June, 2017 at the Department ofPathology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka. The study materials were gastric tissue takenfrom 42 patients who underwent total or partial gastrectomy operation in Surgery Department of BSMMU and few privatehospitals and diagnosed as gastric carcinoma in Pathology department of BSMMU. Result: Among 42 cases, 26 were male and 16 were female with a male/female ratio of 1.6:1. Thirty two samples were totalgastrectomy specimen and twelve samples were partial/subtotal gastrectomy specimen. Ages of the patients ranged from 20 to76 years and the highest number(33.3%) of cases belonged to 50-59 years age group. This study showed E-cadherin expressiondid not show association with lymphovascular invasion, perineural invasion and depth of invasion. The rate of E-Cadherinpositivity shows association with histological type, histological grading and lymph node metastasis. Conclusion: Although alterations in E-cadherin and its expression may serve as promising biomarkers or therapeutic targets ingastric cancer but in this study E-cadherin expression was significantly more frequent in comparison with the histological type,histological grading and lymph node metastasis.

Prognostic significance of E-cadherin expression in prostatic carcinoma: A protocol for systematic review and meta-analysis.

Background:Increasing studies were performed to explore the prognostic value of E-cadherin in prostatic carcinoma, however, with inconsistent results. Hence, this systematic review is aimed to evaluate the prognostic role of E-cadherin in patients with prostatic carcinoma (PCa).Methods:A comprehensive literature search in all available databases will be conducted to identify eligible studies. We will employ hazard ratios (HRs) and 95% confidence intervals (95% CIs) to estimate the correlations between E-cadherin expression and overall survival (OS), disease-free survival (DFS), relapse-free survival (RFS), progression-free survival (PFS) and clinicopathological features. Meta-analysis will be performed using Review Manager (Revman) 5.3.5 software (Cochrane Community, London, United Kingdom) and STATA 14 software (version 14.0; Stata Corp, College Station, TX).Results:This study will provide a high-quality synthesis of current evidence of the correlations between snail expression and OS, DFS/RFS, PFS and clinicopathological features.Conclusion:The study will provide updated evidence to assess whether the expression of E-cadherin is in association with poor prognosis in patients with PCa.Ethics and dissemination:It is not necessary for ethical approval because individuals cannot be identified. The protocol will be disseminated in a peer-reviewed journal or presented at a relevant conference.Prospero registration number:This systematic review protocol has been registered in the PROSPERO network (No. CRD42019128353).

Combined Snail and E-cadherin Predicts Overall Survival of Cervical Carcinoma Patients: Comparison Among Various Epithelial-Mesenchymal Transition Proteins.

BackgroundActivation of Snail and synergistic loss of E-cadherin are hallmark features of the epithelial-mesenchymal transition (EMT), which contributes to the metastasis phenotype of epithelial cancer cells. However, the prognostic impact of Snail and of its combination with E-cadherin and with other EMT prognostic markers has not yet been systematically studied in cervical carcinoma. This study aimed to explore the prognostic value of combined Snail and E-cadherin in patients with cervical carcinoma and compared it to the prognostic value of other EMT prognostic markers.MethodsWe retrospectively identified every initial diagnosis of cervical carcinoma among 203 patients treated at our hospital in China from January 2008 to March 2013. We examined the prognostic significance of Snail and other EMT protein markers, such as E-cadherin, Slug, ZEB1, Twist, Vimentin, and Survivin, by univariate and multivariate survival analyses.ResultsMultivariate analyses showed that Snail and E-cadherin were significant biomarkers for overall survival (OS) in cervical carcinoma patients (HR, hazard ratio = 1.744, P = 0.036 and HR = 1.738, P = 0.047; respectively). Moreover, a combined index including Snail and E-cadherin showed enhanced prognostic value compared to that of Snail or E-cadherin alone. The present data demonstrate that Snail shows a negative correlation with E-cadherin (P < 0.001). High Snail expression and low E-cadherin expression were also more common in high tumor stages (P = 0.044 and P = 0.036; respectively), and lymph node metastasis (both P < 0.001). Moreover, Snail was a superior prognosis factor compared to Slug, ZEB1, Twist, Vimentin, and Survivin in cervical carcinoma.ConclusionBased on our results, Snail and E-cadherin may be considered as independent prognosis markers, and the combination of Snail and E-cadherin might improve the OS prediction accuracy for patients with cervical carcinoma.

High Concentrations of Serum Soluble E-Cadherin in Patients With Q Fever.

Cadherins switching is a hallmark of neoplasic processes. The E-cadherin (E-cad) subtype is one of the surface molecules regulating cell-to-cell adhesion. After its cleavage by sheddases, a soluble fragment (sE-cad) is released that has been identified as a pro-carcinogenic inflammatory signal in several bacteria-induced cancers. Recently we reported that Q fever, a disease due to Coxiella burnetii infection, can be complicated by occurrence of non-Hodgkin lymphoma (NHL). Therefore, we studied E-cad switching in Q fever. The sE-cad levels were found increased in the sera of acute and persistent Q fever patients, whereas they remained at the baseline in controls groups of healthy donors, people cured of Q fever, patients suffering from unrelated inflammatory diseases, and past Q fever patients who developed NHL. These results indicate that sE-cad can be considered as a new biomarker of C. burnetii infection rather than a marker of NHL-associated to Q fever. We wondered if changes in sE-cad reflected variations in the CDH1 gene transcription. The expression of E-cad mRNA and its intracellular ligand β-catenin was down-regulated in peripheral blood mononuclear cells (PBMCs) of patients with either acute or persistent forms of Q fever. Indeed, a lower cell-surface expression of E-cad was measured in a minority (<5%) subpopulation of HLADR+/CD16+ monocytes from patients with acute Q fever. However, a very strong increase in E-cad expression was observed on more than 30% of the HLADR+/CD16+ monocytes of persistent Q fever patients, a cell subpopulation known to be a target for C. burnetii in humans. An experimental in vitro infection of healthy donors' PBMCs with C. burnetii, was performed to directly evaluate the link between C. burnetii interaction with PBMCs and their E-cad expression. A significant increase in the percentage of HLADR+/CD16+ monocytes expressing E-cad was measured after PBMCs had been incubated for 8 h with C. burnetii Nine Mile strain. Altogether, these data demonstrate that C. burnetii severely impairs the E-cad expression in circulating cells of Q fever patients.

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.

Blood serum levels of E-cadherin in patients with colorectal cancer

IntroductionColorectal cancer is the second most common cancer in terms of incidence in Poland. It is also the second most common cause of cancer deaths in men and the third women. In 75–80% of cases, depending on sources, it is of an occasional nature, and in the remaining 20–25% it has a hereditary character.AimTo compare the levels of E-cadherin in blood serum with some histopathological and clinical features. E-cadherin is an adhesion molecule, loss of function of which is suspected to influence both cancer progression and metastasis.Material and methodsThe study group comprised 48 patients diagnosed with colorectal cancer treated surgically in the Second Department of General and Gastroenterological Surgery, Medical University Hospital in Bialystok.ResultsAs has been shown here, there is no statistically significant relationship between the levels of E-cadherin in blood serum and the possible prognosis to the progression of colorectal cancer. However, it was indicated that there appears to be a statistically significant relationship between blood serum E-cadherin levels and the levels of alanine aminotransferase and aspartate aminotransferase in patients with colorectal cancer.ConclusionsThe authors suggest that this significance may require further study.

Expression and Prognostic Significance of E-Cadherin in Patients with Colorectal Adenocarcinoma: Results from a Retrospective Study

Expression and Prognostic Significance of E-Cadherin in Patients with Colorectal Adenocarcinoma: Results from a Retrospective Study

Clinical Significance of SIP1 and E-cadherin in Patients with Esophageal Squamous Cell Carcinoma.

Epithelial-mesenchymal transition (EMT), when epithelial cells convert to mesenchymal cells, influences cancer invasion and metastasis. Smad interacting protein 1 (SIP1) is an EMT trigger, which is inversely correlated with E-cadherin in some carcinomas. To elucidate the role of SIP1 in esophageal squamous cell carcinoma (ESCC), the status of EMT and the clinicopathological features were evaluated. Immunohistochemical (IHC) analyses of 111 human ESCC tissue specimens for SIP1 and E-cadherin were performed, and the relationships between the expression and clinicopathological features were evaluated. IHC analyses of esophageal tumors showed the expression of SIP1 and E-cadherin to be significantly inversely correlated. Significant correlations between the SIP1 expression and clinicopathological variables such as differentiation, depth of invasion, vascular invasion, and pathological stage were also seen. Conversely, tumors with a weak expression of E-cadherin tended to exhibit greater histological differentiation. Logistic regression analyses revealed a positive SIP1 expression, lymphatic invasion, and vascular invasion to be factors predicting lymph node (LN) metastasis. Univariate survival analyses revealed a positive SIP1 expression predicted a poorer overall survival than a negative expression. These results suggest that SIP1 is correlated with LN metastasis and may therefore be an independent marker for metastasis in patients with ESCC.

Prognostic evaluation of Nanog, Oct4, Sox2, PCNA, Ki67 and E-cadherin expression in gastric cancer.

The purpose of this study was to evaluate expression and prognostic impact of Nanog, Oct4, Sox2, proliferation cell nuclear antigen (PCNA), Ki67 and E-cadherin in patients with gastric cancer (GC) by immunohistochemistry. A total of 69 patients were recruited who underwent gastrectomy between 2008 and 2009. We found that expression levels of Nanog, Oct4, Sox2, PCNA, Ki67 and E-cadherin were 26.1, 53.6, 49.3, 52.2, 60.9 and 60.9%, respectively. Co-expression of more than any two proteins (defined as high-risk group) was detected in 43 of 69 (62.3%) patients with GC. Only positive expression of Oct4 had relationship with lymphatic invasion (p=0.013), and positive expression of Ki67 was correlated with T classification (p=0.011). Furthermore, positive expression of Oct4 (p=0.043), PCNA (p=0.035) and Ki67 (p=0.023) was significantly associated with poor 3-year disease-free survival (DFS). The same result was detected in patients with E-cadherin reduced expression (p=0.022). But only PCNA positive expression predicted poor overall survival (p=0.042) in univariate analysis. In addition, 3-year DFS was 20% in high-risk group and 71% in low-risk group. The same tendency was found between OS and co-expression of proteins. There was a remarkable difference between DFS or OS and co-expression of more than two proteins (p=0.000). Multivariate analysis showed that E-cadherin and co-expression were independent prognostic factors of 3-year diseases-free survival. But only co-expression of more than two markers dramatically affected the survival of GC patients. These findings provide evidence that combined evaluation of Nanog, Oct4, Sox2, PCNA, Ki67 and E-cadherin may be a more powerful prognostic factor to predict relapse and distant metastasis for patients with GC.

Prognostic and Clinicopathological Significance of Downregulated E-Cadherin Expression in Patients with Non-Small Cell Lung Cancer (NSCLC): A Meta-Analysis

BackgroundMany studies have investigated the prognostic role of E-cadherin in patients with NSCLC; however, the result still remains inconclusive. An up-to data system review and meta-analysis was necessary to give a comprehensive evaluation of prognostic role of E-cadherin in NSCLC.MethodsEligible studies were searched in Pubmed, Embase and Web of Science databases. The inclusion criteria were studies that assessed the relationship between E-cadherin expression detected by immunohistochemistry (IHC) and the prognosis or clinicopathological features in patients with NSCLC. Subgroup analysis according to race, percentage of reduced/negative E-cadherin expression, histological type, and sample size were also conducted. Odds ratio (OR) or hazard ratio (HR) with 95% confidence interval (CI) were calculated to examine the risk or hazard association.ResultsA total of 29 studies including 4010 patients were qualified for analysis. The analysis suggested that downregulated E-cadherin expression was significant associated with unfavorable overall survival (OS) and disease-free survival/progression-free survival (DFS/PFS) in patients with NSCLC. Subgroup analysis by race, percentage of reduced/negative E-cadherin expression, sample size also found the significant association in OS. When only the stage I NSCLC were considered, downregulated E-cadherin expression still had an unfavorable impact on OS. Additionally, downregulated E-cadherin expression was significantly associated with differentiation grade, lymphnode metastasis, vascular invasion, and TNM stage.ConclusionDownregulated E-cadherin expression detected by IHC seems to correlate with tumour progression and could serve as an important prognostic factor in patients with NSCLC.

Alteration of Urothelial Inflammation, Apoptosis, and Junction Protein in Patients with Various Bladder Conditions and Storage Bladder Symptoms Suggest Common Pathway Involved in Underlying Pathophysiology.

Lower urinary tract symptoms (LUTS) are common in various bladder disorders. This study investigated urothelial dysfunction and chronic inflammation in the urothelium in different types of lower urinary tract dysfunction (LUTD), which causes bladder storage symptoms. Bladder tissues were obtained from patients with LUTD including 17 with interstitial cystitis/bladder pain syndrome (IC/BPS), 15 with bladder outlet obstruction (BOO), 12 with spinal cord injury (SCI), 12 with recurrent urinary tract infection (UTI), 13 with ketamine related cystitis (KC) and 10 controls. The bladder specimens were investigated using immunofluorescence (IF) staining of the urothelial junction protein E-cadherin and the TUNEL assay for urothelial apoptosis. Mast cell activation was also measured by IF using tryptase for mucosal inflammation. Statistical analysis was performed using the Kruskal-Wallis and Wilcoxon rank-sum test and P-values less than 0.05 were considered significant. Highly significant increases of mast cell infiltration were observed in patients with KC (7.8 ± 3.7), IC/BPS (4.6 ± 3.0), recurrent UTI (2.4 ± 1.2), SCI (3.7 ± 2.7), and BOO (5.1 ± 2.0) compared with controls (1.3 ± 1.2) (all p < 0.05). Statistically significant increases of apoptotic cells were observed in patients with KC (4.2 ± 1.5), IC/BPS (2.4 ± 1.7), SCI (2.4 ± 1.4), recurrent UTI (1.9 ± 2.4), and BOO (1.2 ± 1.1) compared with controls (0.08 ± 0.3) (all p < 0.05). Significantly decreased expression of E-cadherin in patients with IC/BPS (25.1 ± 16.3), KC (11.0 ± 11.3), and recurrent UTI (26.2 ± 5.0) was found compared to controls (42.4 ± 16.7) and patients with SCI (44.4 ± 18.8) or BOO (42.8 ± 14.3) (all P < 0.05). Increased urothelial inflammation and urothelial cell apoptosis seem to share common pathophysiologies of various LUTDs that cause similar bladder symptoms.

Aberrant Expression of Hypoxia-inducible Factor 1 , TWIST and E-cadherin is Associated with Aggressive Tumor Phenotypes in Endometrioid Endometrial Carcinoma

Intratumoral hypoxia promotes angiogenesis, invasion and epithelial-mesenchymal transition, a pivotal event in tumor metastasis. TWIST is a master regulator of multiple developmental processes and has recently been shown to be the key factor responsible for cancer metastasis via the inhibition of E-cadherin expression, a hallmark of epithelial-mesenchymal transition. This study aimed to determine the expression of hypoxia-inducible factor 1α, TWIST and E-cadherin in patients with endometrioid endometrial carcinoma and to examine their clinical significance in endometrioid endometrial carcinoma progression. Using immunohistochemical and tissue microarray approaches, we evaluated the expression of hypoxia-inducible factor 1α, TWIST and E-cadherin in normal endometrial (n = 35), atypical hyperplasia (n = 28) and endometrioid endometrial carcinoma samples (n = 124). Furthermore, we statistically analyzed the association between these markers, as well as their correlation with clinicopathologic variables. The expression of hypoxia-inducible factor 1α and TWIST were markedly increased, whereas E-cadherin was decreased, as lesions progressed from normal endometrium to atypical hyperplasia to carcinoma (P < 0.01). Among various clinical parameters, the expression of hypoxia-inducible factor 1α and TWIST was strikingly elevated with aggressive tumor characteristics, including higher pathologic grade, deep myometrial invasion and lymph node involvement (P < 0.05). More importantly, overexpression of hypoxia-inducible factor 1α positively correlated with enhanced TWIST expression in endometrioid endometrial carcinoma samples (r = 0.249, P < 0.01); however, statistical analysis showed a negative relationship between TWIST upregulation and E-cadherin downregulation (r = -0.183, P = 0.042). These results demonstrated for the first time that the hypoxia-inducible factor 1α/TWIST/E-cadherin pathway may play a critical role in invasion and metastasis of endometrioid endometrial carcinoma. The combined evaluation of these markers may be useful in predicting aggressive phenotypes and thus prognosis in patients with endometrioid endometrial carcinoma.

Prognostic role of E-cadherin in patients with advanced serous ovarian cancer

To analyse correlation between expression of E-cadherin and clinical and pathological features and overall survival in advanced-stage serous ovarian carcinoma. The expression of E-cadherin was analysed immunohistochemically in formalin-fixed, paraffin-embedded samples from 54 patients with advanced-stage serous ovarian cancer and related to clinicopathological characteristics and patients survival. The clinicopathological characteristics included the stage according to the International Federation of Gynecology and Obstetrics (FIGO), tumour differentiation, number of mitoses per 10 high-power fields (HPF), residual tumour size, and vascular invasion. Only patients with serous ovarian cancer FIGO stages III-IV were included. Overall survival (OS) was defined as time from surgery to the last follow-up date on 01.10.2010. OS was evaluated using Kaplan-Meier method, and log-rank test was used to asses the differences between the positive and E-cadherin negative group. Multivariate analysis was completed using the Cox proportional hazard regression model. E-cadherin immunoreactivity was not associated with FIGO stage, tumour grade, number of mitotic figures per 10 HPF, residual tumour volume or vascular invasion. Negative E-cadherin expression significantly predicted shorter OS (p<0.001). The multivariate analyses showed that negative E-cadherin (p<0.001), FIGO stage (p=0.012) and residual tumour size >1cm after the initial cytoreductive surgery (p<0.001) were predictors of shorter OS. Negative E-cadherin expression like presence of residual tumour after primary cytoreductive surgery and higher FIGO stage seem to predict unfavourable clinical outcome in patients with advanced-stage serous ovarian cancer. Negative expression of E-cadherin was shown to be a significant independent predictor of poorer OS. E-cadherin as marker has prognostic value.

Prognostic value of Twist and E-cadherin in patients with osteosarcoma

Twist, a basic helix-loop-helix transcription factor, and E-cadherin are both correlated with the metastatic progression of several types of cancer. However, it is currently unknown whether their activations have relevance to the progression of osteosarcoma. The purpose of the present study was to investigate the clinicopathological and prognostic value of Twist and E-cadherin in osteosarcoma. Twist and E-cadherin expressions were determined by immunohistochemistry. Patient survival rates were determined by Kaplan-Meier method and log-rank test. Cox regression was adopted for multivariate analysis of prognostic factors. The positive rates of Twist and E-cadherin in 107 osteosarcoma specimens were 31.8 % (34/107) and 20.6 % (22/107), respectively. Twist expression was significantly correlated with that of E-cadherin (r = -0.209, P = 0.031). The positive expression of Twist and E-cadherin was significantly associated with metastasis in 107 osteosarcoma specimens (both P < 0.05). Patients with positive Twist expression had significantly poorer overall survival (OS; P < 0.05) and disease-free survival (DFS, P < 0.05) when compared with patients with the negative expression of Twist. Patients with positive expression of E-cadherin had significantly poorer OS (P < 0.05) when compared with patients with negative E-cadherin expression, but not a significantly poorer DFS (P = 0.081). On multivariate analysis, Twist expression and age were found to be independent prognostic factors for OS (both P < 0.05) and DFS (both P < 0.05). Our results suggest that Twist was expressed significantly more and E-cadherin significantly less in osteosarcoma with metastasis, and expression of both might be related to the prediction of metastasis potency and poor prognosis for patients with osteosarcoma.