Clinical significance of dysadherin expression in gastric cancer patients.

PURPOSE: Dysadherin, a cancer-associated cell membrane glycoprotein, has been reported to down-regulate E-cadherin expression and promote metastasis. To evaluate the role of dysadherin in gastric cancer, we examined dysadherin and E-cadherin expression in gastric cancer patients. EXPERIMENTAL DESIGN: Dysadherin and E-cadherin expression were evaluated in 276 gastric cancer patients by immunohistochemistry, and the results were compared with the clinicopathological findings of the subjects. RESULTS: Dysadherin was not expressed in normal gastric epithelium. Both dysadherin and E-cadherin were localized to the cell membrane. Dysadherin expression was sometimes largely localized to infiltrating tumor cells or cells dissociating. Ninety gastric cancer patients (32.6%) were positive for dysadherin, and 151 patients (54.7%) showed preservation of E-cadherin expression. Expression of dysadherin was associated with moderately differentiated carcinoma and hematogenous metastasis, whereas reduced expression of E-cadherin showed an association with poorly differentiated carcinoma and peritoneal dissemination. As a result, dysadherin positivity and reduced E-cadherin expression were associated with a poor prognosis. In addition, patients with both dysadherin positivity and reduced E-cadherin had the worst prognosis. Multivariate analysis revealed that reduced E-cadherin expression was an independent prognostic factor, but dysadherin expression was not. CONCLUSION: Combined analysis of dysadherin and E-cadherin expression may help to predict the prognosis and the mode of metastasis in gastric cancer patients. Patients with dysadherin positivity have a higher risk of hematogenous metastasis, whereas patients with reduced E-cadherin expression have an increased risk of peritoneal dissemination.     

Clinicopathologic significance of dysadherin expression in cutaneous malignant melanoma: immunohistochemical analysis of 115 patients

BACKGROUND: The E-cadherin-mediated cell adhesion system is frequently inactivated by multiple mechanisms and is involved in tumor progression in many types of cancer. Recently, the authors reported a novel cell membrane glycoprotein, dysadherin, which has an anti-cell-cell adhesion function and down-regulates E-cadherin. METHODS: Expression of both dysadherin and E-cadherin was investigated immunohistochemically in 115 patients with cutaneous malignant melanoma to determine the correlation between the 2 molecules and their associations with both patient survival and the clinicopathologic features of the tumors. RESULTS: Dysadherin and E-cadherin were expressed at the cell membranes of melanoma cells. Fifty-two percent of the tumors showed dysadherin immunopositivity, and 91% of the tumors showed reduced E-cadherin immunopositivity. There was no significant inverse correlation between dysadherin expression and E-cadherin expression. Increased dysadherin expression was significantly correlated with nodular subtype (P = 0.042), Clark level (P < 0.001), tumor thickness (P < 0.001), ulceration (P = 0.008), lymph node metastasis (P < 0.001), high TNM classification (P < 0.001), and poor patient survival (P < 0.001). Multivariate analysis of patient survival revealed that increased dysadherin expression was a significant predictor of poor survival (P < 0.001). CONCLUSIONS: Thus, increased expression of dysadherin was a significant indicator of poor prognosis in patients with cutaneous malignant melanoma.     

Prognostic significance of dysadherin expression in cervical squamous cell carcinoma

The protein and mRNA expression of dysadherin was studied in a series of squamous cell cervical carcinomas, and their clinicopathological associations and prognostic value were explored. Immunohistochemistry was used to assess protein expression of dysadherin in 206 patients with squamous cell cervical carcinoma, FIGO stage Ia-IVb. Frozen tissues from 20 cases in which the tumors showed variable dysadherin protein expression were used for laser capture microdissection (LCM) and processed for RTPCR detection of dysadherin mRNA. Immunohistochemically, all the dysadherin-positive staining was membranous. Positive cell membranous dysadherinpositive staining was often observed at the edge of tumor nests, although strong immunoreactivity throughout whole tumor nests was also seen in some tumors. Basal cells of the normal cervical epithelia were positive for dysadherin while its expression in the squamous cell cervical carcinomas was variable. Among the 206 tumors, 23 (11.2%) were negative, 53 (25.7%) were scored 1+, 54 (26.2%) were scored 2+ and 76 (36.9%) were scored 3+. In the 20 tumors analyzed, mRNA expression of dysadherin basically corresponded to its protein expression. No significant correlation between expression of dysadherin and age, FIGO stage or lymph node status was observed. Higher level of dysadherin expression, however, was significantly associated with shorter overall survival (p=0.04). We conclude that there is dysadherin protein expression in basal and parabasal cells of normal cervical epithelia, and higher level of dysadherin protein expression in squamous cell cervical carcinoma is predictive of a shorter overall survival, indicating that dysadherin may be a valuable prognostic marker in cervical carcinoma.     

Prognostic significance of tissue factor in pancreatic ductal adenocarcinoma.

Tissue factor (TF) is a transmembrane glycoprotein that plays roles in the blood coagulation and intracellular signaling pathways, and has also been suggested to modulate the biological behavior of cancer cells. In order to examine the clinicopathologic significance of TF expression in pancreatic ductal adenocarcinoma, TF expression was determined by immunohistochemistry using a newly raised anti-TF monoclonal antibody in 113 patients who had undergone surgical resection of pancreatic ductal adenocarcinoma. According to the incidence of tumor cell immunopositivity, patients were divided into "negative TF" (0%), "weak TF" (<25%), or "high TF" (25% or more) groups, which accounted for 11.6% (n = 13), 44.2% (n = 50), and 44.2% (n = 50) of the total, respectively. Increased TF expression was correlated with the extent of the primary tumor (P = 0.0043), lymph node metastasis (P = 0.0043), lymphatic distant metastasis (P = 0.0039), advanced tumor-node-metastasis stage (P = 0.0002), and high tumor grade (P = 0.0164). Multivariate analysis using the Cox proportional hazards model showed that high TF expression was an independent negative predictor for survival (hazard ratio, 2.014; P = 0.0076). Moreover, patients with TF-negative tumors had a significantly better prognosis even if lymph node metastasis was present (P < 0.0001). We also showed that TF knockdown by RNA interference suppressed the invasiveness of a pancreatic adenocarcinoma cell line in vitro. These results indicate that TF expression may contribute to the aggressiveness of pancreatic ductal adenocarcinoma by stimulating tumor invasiveness, and that evaluation of the primary tumor for TF expression may identify patients with a poor prognosis.     

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.     

iNOS、COX-2在胰腺癌组织中的表达及其临床意义

 目的　探讨诱导型一氧化氮合酶 (iNOS )和环氧化酶 2 (COX 2 )在胰腺癌组织中的表达及其与生物学行为之间的关系。方法　用免疫组织化学EnVision法对 5 1例胰腺导管癌iNOS和COX 2的表达进行检测。结果　 5 1例胰腺导管癌中iNOS蛋白和COX 2蛋白的阳性表达率分别为 6 2 .7%、74 .5 % ;二者在 11例癌旁非肿瘤胰腺组织中均不表达。iNOS的表达与淋巴结转移有关 (P <0 .0 1) ,而与肿瘤组织学分级、临床分期无关 (P >0 .0 5 ) ;COX 2的表达与临床分期、淋巴结转移有关 (P <0 .0 5 ) ,而与组织学分级无关 (P >0 .0 5 ) ;iNOS的表达与COX 2的表达密切相关 (P <0 .0 5 )。结论　iNOS和COX 2可能在胰腺癌的发生、发展过程中起协同作用 ,促进肿瘤的血管生成和转移。     

Epithelial-cadherin and beta-catenin expression changes in pancreatic intraepithelial neoplasia.

PURPOSE: Cadherins and associated catenins are important mediators of epithelial cell-cell adhesion, as well as the Wnt-signaling pathway. Significant changes in their expression or structure have been implicated in malignancy. This study aimed to investigate the epithelial-cadherin (E-cadherin) and beta-catenin expression changes during multistage, pancreatic ductal carcinogenesis. EXPERIMENTAL DESIGN: Ninety-four Whipple resection specimens were retrieved from the surgical pathology files of the University Health Network (Toronto, Canada), from which tissue microarray blocks containing 36 pancreatic ductal adenocarcinomas, 34 PanIN-1A lesions, 28 PanIN-1B lesions, 27 PanIN-2 lesions, 16 PanIN-3 lesions, and 32 normal ducts were constructed. The E-cadherin, beta-catenin, and the phosphorylated glycogen synthase kinase-3beta of the Wnt/beta-catenin pathway were immunohistochemically evaluated in these duct/PanIN lesions. RESULTS: There was marked increase in the cytoplasmic E-cadherin expression in PanIN lesions (P < 0.0001) and adenocarcinoma (P = 0.005) compared with normal pancreatic ducts. In contrast, reduced/loss of E-cadherin membranous expression was also significant in ductal adenocarcinoma compared with both the PanIN lesions (P < 0.0001) and normal ducts (P = 0.05). The beta-catenin expression showed significantly more frequent aberrant nuclear localization in high-grade PanIN lesions, particularly PanIN2 and in adenocarcinoma compared with normal ducts or low grade PanIN lesions (P < 0.0001). However, there was a lack of correlation between phospho(Ser9)-glycogen synthase kinase-3beta cytoplasmic expression and beta-catenin aberrant nuclear expression (P = 0.07). CONCLUSIONS: Aberration in the expression of E-cadherin and its associated beta-catenin is evident in pre-invasive (PanIN) neoplastic pancreatic duct cells, suggesting involvement of pathways leading to beta-catenin stabilization during pancreatic duct cell carcinogenesis.     

浸润性乳腺导管癌组织中Ezrin和钙粘素E的表达与淋巴结转移的关系

背景与目的：Ezrin是一种细胞骨架连接蛋白,参与调节肿瘤细胞的生长和转移。本研究通过检测Ezrin和钙粘素E（E-cadherin）在浸润性乳腺导管癌中的表达情况,探讨其在淋巴结转移中的意义。方法：采用免疫组织化学SP法检测60例浸润性乳腺导管癌病理组织切片中Ezrin和E-cadherin的表达。结果：Ezrin在37例无转移的癌组织中19例异常表达（51．35％）。23例有转移的癌组织中17例异常表达（73．91％）。E-cadherin在无转移的癌组织中15例异常表达（40．54％）。而在有转移的癌组织中15例异常表达（65．22％）。Ezrin异常表达与E-cadherin异常表达有显著的正相关性（r=0．898,P=0．038）。结论：Ezrin和E-cadherin与乳腺导管癌的浸润和转移密切相关,可以作为预测浸润性乳腺导管癌淋巴结转移的重要肿瘤标志物。     

Prognostic significance of dysadherin expression in advanced colorectal carcinoma

A novel glycoprotein, dysadherin, has an anti-cell - cell adhesion function through downregulating E-cadherin. In this study, we investigated the expressions of dysadherin and E-cadherin in 82 patients with stage II and III colorectal carcinomas to determine the correlation between the two molecules and the clinicopathologic features of each tumour. Dysadherin was not expressed in normal colorectal epithelium. Fifty-one per cent of tumours showed dysadherin immunopositivity in over 50% of cancer cells. Thirty-eight per cent of tumours showed reduced E-cadherin immunopositivity. The increased expression of dysadherin was significantly associated with lung metastasis (P=0.003). The increased expression of dysadherin had a significant impact on patient survival (P=0.0099 and 0.0036, log-rank test for overall and recurrence-free survival rate, respectively). Furthermore, tumour with increased expression of dysadherin and reduced expression of E-cadherin showed the worst prognosis (P=0.0043 and 0.0028, log-rank test for overall and recurrence-free survival rate, respectively). These results suggest that increased dysadherin expression is a significant indicator of poor prognosis for patients with advanced colorectal carcinoma.     

Prognostic significance of dysadherin expression in esophageal squamous cell carcinoma

OBJECTIVE: Dysadherin is a cancer-associated cell membrane glycoprotein that has been reported to downregulate E-cadherin expression and promote metastasis. To evaluate the role of dysadherin in metastasis of esophageal squamous cell carcinoma (ESCC), we examined dysadherin and E-cadherin expression in patients with this cancer. METHODS: Dysadherin and E-cadherin expression was evaluated in 117 ESCC patients (pT1, 31; pT2, 30; pT3, 39; pT4, 17) by immunohistochemistry. The findings were compared with the clinicopathological data of the patients. RESULTS: Both dysadherin and E-cadherin were localized to the cell membrane. Thirty patients (29.1%) had tumors positive for dysadherin and 41 patients (35.0%) had tumors positive for E-cadherin. Tumors showing dysadherin positivity and negative E-cadherin expression had a significantly worse prognosis than other tumors. When the patients with dysadherin- positive tumors were combined with E-cadherin-negative patients, this group had a worse prognosis (p < 0.0001). Cox multivariate analysis revealed that dysadherin expression was an independent prognostic factor for ESCC (p = 0.003), but E-cadherin expression was not. CONCLUSION: Combined analysis of dysadherin and E-cadherin expression may help to predict the prognosis of patients with ESCC. Our results suggested that expression of dysadherin by this cancer may partly explain the poor prognosis of patients with preservation of E-cadherin expression.     

胰腺导管腺癌中酪氨酸蛋白激酶-7的表达及临床意义

  目的  探讨酪氨酸蛋白激酶-7(protein tyrosine kinase-7, PTK7)在胰腺导管腺癌组织中的表达及其临床意义。  方法   回顾性分析天津医科大学肿瘤医院2011年5月至2016年1月接受胰腺癌根治手术治疗的85例胰腺癌患者的临床与随访资料。采用免疫组织化学法检测85例胰腺癌组织和对应的癌旁组织中PTK7的表达, 分析其与临床病理学特征及预后的关系。  结果  PTK7的阳性表达主要在细胞质内, 呈棕黄色颗粒。PTK7在胰腺癌和癌旁组织中的阳性表达率分别为70.6%(60/85)和52.9%(45/85), 前者表达率显著高于后者, 差异具有统计学意义(P < 0.05)。PTK7的异常表达与肿瘤分期、淋巴结转移和脉管内瘤栓相关(P < 0.05)。生存分析提示在胰腺导管腺癌中PTK7高表达的患者生存时间和肿瘤无进展时间明显短于低表达的患者(均P < 0.05)。shRNA成功干扰PTK7建立细胞稳系后, MTT和克隆形成结果显示, shRNA实验组较对照组细胞存活数显著减少(P < 0.05), 克隆形成数显著减少(P < 0.05), 增殖相关蛋白Ki67和PCNA的表达水平显著降低(均P < 0.05)。  结论   胰腺导管腺癌组织中PTK7表达水平上调, 且与胰腺癌肿瘤分期、淋巴结转移、脉管内瘤栓有关, 其表达可能提示预后不良。在胰腺癌细胞系中, PTK7能通过调节增殖相关因子Ki-67和PCNA的水平而促进胰腺癌细胞的增殖。      

角质细胞生长因子及E-钙黏蛋白在胰腺癌组织中的表达及其意义

目的 研究角质细胞生长因子(KGF)及E-钙黏蛋白(E-cadherin)在胰腺癌组织中的表达及其临床意义.方法 应用免疫组织化学SP法检测45例胰腺癌组织、22例癌旁正常胰腺组织中KGF及E-cadherin的表达,并结合临床病理资料进行分析.结果 KGF在胰腺癌组织阳性表达率为77.8%(35/45),比相应的癌旁正常胰腺组织表达明显增高,且与癌组织分化程度及临床分期相关(P值均＜0.05);E-cadherin在胰腺癌组织比相应的癌旁正常胰腺组织表达减低,高表达率为35.6%(16/45),且与癌组织分化程度、淋巴结转移及临床分期密切相关(分别为P＜0.05,P＜0.05,P＜0.01);在胰腺癌组织中,KGF与E-cadherin表达呈负相关(P＜0.01).结论 KGF与E-cadherin有望作为胰腺癌的增生、分化、侵袭以及转移的重要生物学指标.     

Loss of E-cadherin expression correlates with poor differentiation and invasion into adjacent organs in gastric adenocarcinomas

Perturbation in E-cadherin expression leads to loss of cellular adhesion with possible consequence of cellular transformation and tumor progression. The aims of this study were to determine E-cadherin expression in each subtype of gastric cancer classified by different classification systems, and to investigate the role of E-cadherin in cell differentiation, cancer invasion and metastasis. Expression of E-cadherin was analyzed in 84 patients with gastric adenocarcinoma by immunohistochemistry and correlated with clinicopahotlogical parameters. Our results showed loss of E-cadherin expression in 0% (0/3), 20.0% (9/45), 48% (15/31), 100% (3/3) and 100% (2/2) of papillary, tubular, poorly differentiated, signet-ring cell, and mucinous adenocarcinoma by Japanese histological classification. The reduction of E-cadherin expression was inversely correlated with the grade of differentiation. According to the histological classification of Lauren and Ming, the frequency of lost E-cadherin expression was higher in diffuse type (65%) and infiltrative type (64%) gastric cancer than in intestinal type (20%, P<0.001) and expanding type cancer (22%, P<0.001), respectively. The loss of E-cadherin expression was significantly associated with tumor invasion (P<0.05). Furthermore, there was a borderline association between the loss of E-cadherin expression and poor survival (P=0.109). These data demonstrated a striking correlation between E-cadherin expression and the differentiation of gastric carcinoma. The loss of E-cadherin expression may contribute to gastric cancer invasion to adjacent organs.     

Cytoplasmic expression of laminin gamma2 chain correlates with postoperative hepatic metastasis and poor prognosis in patients with pancreatic ductal adenocarcinoma

BACKGROUND: The laminin gamma2 chain is involved in tumor invasion and metastasis, but the significance of laminin gamma2 chain expression remains unclear in patients with pancreatic carcinoma. METHODS: Laminin gamma2 chain expression was examined immunohistochemically in 48 patients with pancreatic ductal adenocarcinoma who were followed closely to elucidate the correlations between clinicopathologic factors, postoperative recurrence, and overall survival. Prognostic factors for postoperative survival were examined comparing clinicopathologic factors and laminin gamma2 chain expression. RESULTS: Two different staining patterns of laminin gamma2 chain expression, cytoplasmic expression and basement membrane expression, were detected in tumors from all 48 patients. Tumors were then classified into two types according to the dominant pattern of laminin gamma2 chain expression: the cytoplasmic expression dominant type (CYT; n = 26 patients) and the basement membrane expression dominant type (BM; n = 22 patients). Tumor differentiation was associated statistically with the BM type of laminin gamma2 chain expression (P = 0.0002). The CYT type of laminin gamma2 chain expression was associated significantly with the occurrence of postoperative hepatic metastasis (P = 0.0011) and also was the strongest predictive factor for poorer overall survival in patients with pancreatic ductal adenocarcinomas (P = 0.0161). CONCLUSIONS: The cytoplasmic expression of the laminin gamma2 chain represents the high invasive potential of the tumor and is correlated with distant metastasis, especially hepatic metastasis, and with a poorer prognosis in patients with pancreatic ductal adenocarcinoma.     

High expression of vascular endothelial growth factor is associated with liver metastasis and a poor prognosis for patients with ductal pancreatic adenocarcinoma

BACKGROUND: Vascular endothelial growth factor (VEGF), a recently identified growth factor with significant angiogenic properties, is a multifunctional angiogenic cytokine that is expressed in many tumors. High VEGF expression has been shown to correlate with the incidence of metastasis and poor prognosis in various cancers. In this study, the authors investigated VEGF expression and microvessel density (MVD) in ductal pancreatic adenocarcinoma and examined the correlations among VEGF expression, clinicopathologic factors, and clinical outcome. The authors especially focused on the correlation between VEGF expression and liver metastasis. METHODS: Paraffin embedded tumor specimens of 142 surgically resected pancreas carcinoma were immunohistochemically stained for VEGF and MVD. The correlations among VEGF expression and MVD, clinicopathologic factors, and clinical outcome were then statistically analyzed. RESULTS: One hundred thirty-two (93%) of 142 ductal pancreatic adenocarcinomas were positive for VEGF protein by immunohistochemistry. A significant correlation was observed between VEGF positivity and MVD (P < 0.0001). Multivariate logistic regression analysis indicated a significant association between high VEGF expression and liver metastasis (P = 0.010) but no other factors, such as age, tumor size, histologic type, lymph node metastasis, venous invasion, neural invasion, peritoneal metastasis, or local recurrence. Patients with tumors that showed moderate or high VEGF expression had significantly shorter survival than patients with low VEGF expression or none at all in their tumors (P < 0.05). CONCLUSIONS: These results indicate that VEGF expression is closely correlated with MVD and seems to be an important predictor for both liver metastasis and poor prognosis in ductal pancreatic adenocarcinoma.     

Clinicopathological significance of galectin-3 expression in ductal adenocarcinoma of the pancreas.

PURPOSE: Galectin-3, a member of the beta-galactoside-binding lectin family, has multiple biological functions including cell-cell interactions and cell-extracellular matrix adhesion, cellular proliferation, cellular differentiation, and apoptosis. The aim of this study was to determine the relationship of galectin-3 expression to clinicopathological findings and patient prognosis in ductal adenocarcinoma of the pancreas. EXPERIMENTAL DESIGN: We examined galectin-3 expression in 104 surgically resected pancreatic ductal adenocarcinoma cases with stages I through IV using immunohistochemistry and investigated the relationship of it to overall survival. RESULTS: Patients were divided into two groups: a low expression group, where <60% of tumor cells were positive; and a high expression group, where > or =60% of tumor cells were positive. Cases in the low expression group had a significant tendency to be at later stages, to have distant metastasis, and to have less differentiated tumors, compared with cases in the high expression group (P = 0.001 for stage, P = 0.001 for metastasis, and P = 0.006 for differentiation). Postoperative overall survival was worse in the low galectin-3 expression group than in the high galectin-3 expression group (P = 0.004). Multivariate analysis showed that the risk ratio of prognosis was 2.06 among patients in the low galectin-3 expression group compared with the high galectin-3 expression group (P = 0.006). CONCLUSIONS: Decreased expression of galectin-3 was associated with advanced stage, tumor de-differentiation, and metastasis in ductal adenocarcinoma of the pancreas. Galectin-3 expression might be a useful prognostic marker for survival in ductal adenocarcinoma of the pancreas.     

Dysadherin expression facilitates cell motility and metastatic potential of human pancreatic cancer cells

Dysadherin is a membrane glycoprotein expressed strongly in several human cancers. Overexpression of dysadherin in tumor cells is closely associated with malignant phenotype (e.g., metastasis) and poor prognosis. In our analysis, six pancreatic cancer cell lines showed a positive correlation between dysadherin expression and cell motility. Introduction of small interfering RNA (siRNA) against dysadherin into the Panc-1 cell line caused reduction of dysadherin expression and suppression of cell motility. In contrast, stable transfection of a dysadherin expression vector into the Capan-1 cell line increased cell motility. In vivo, the metastatic potential of orthotopically transplanted Capan-1 tumor cells in severe combined immunodeficient mice was increased by dysadherin overexpression. Cell morphology and actin organization were also influenced by modulation of dysadherin expression. Cells transfected with dysadherin siRNA tended to have a relatively larger, more spread shape and increased transverse actin stress fibers compared with parent cells and cells transfected with control siRNA. Our study suggests that dysadherin is able to modulate actin structures, stimulate cell motility, and contribute directly to the metastatic potential of human pancreatic cancer cells.