Epithelial Syndecan-1 Research Articles

Intestinal barrier biomarkers in clinical evaluation of patients with inflammatory bowel disease.

Inflammatory bowel disease (IBD) is associated with chronic intestinal barrier dysfunction, though its non-invasive assessment remains challenging. This study aimed to determine how four putative circulating markers vary across differing states of intestinal inflammation and with therapy in patients with IBD. Plasma samples from one prospective cross-sectional and four longitudinal studies, including healthy controls, were analysed for markers of lipopolysaccharide translocation, lipopolysaccharide-binding protein (LBP) and soluble-CD14 (sCD14), and markers of epithelial injury, syndecan-1 and intestinal-type fatty acid-binding protein (IFABP). Inflammatory activity was determined using objective measures. Compared with healthy subjects, concentrations of LBP and sCD14 were higher in patients with active (P < 0.001) and severe ulcerative colitis (UC) (P < 0.0001) and active Crohn's disease (CD) (P < 0.001). In UC in remission, LBP was less than in active disease (P = 0.011) LBP levels decreased longitudinally before and after induction of medical therapy in patients with IBD (P = 0.030) and as severe UC was brought into remission at weeks 2 and 12 (P ≤ 0.022). Response to treatment was associated with higher baseline levels of LBP (P = 0.019) and soluble-CD14 (P = 0.014). Concentrations of syndecan-1 and IFABP were or tended to be lower in UC and CD in active disease and did not change with successful therapy. While markers of epithelial injury were subnormal with active disease and did not change with therapy, markers of lipopolysaccharide translocation directly reflected intestinal inflammation, reduced with successful therapy and predicted treatment response.

Stromal and epithelial syndecan-1 expression in benign and malignant salivary gland tumors: which is more reflective of behavior?

IntroductionSalivary gland tumors are a diverse group of lesions, with various origins and extremely different behaviors, leading to a variety of outcomes for patients. Therefore, the need to discover novel markers with the ability to predict the behavior of benign and malignant salivary gland neoplasms is crucial. Syndecan-1 is a cell-surface protein with significant roles in various aspects of tumor function. Its expression in salivary gland neoplasms, especially their stromal component, has not been investigated. ObjectivesWe aimed to assess the immunopositivity of syndecan-1 in epithelial and stromal components of salivary gland neoplasms and to compare it between benign and malignant subtypes in addition to evaluating its correlation with clinicopathologic parameters. Methods133 salivary gland tumors were immunohistochemically stained with syndecan-1 and the intensity and percentage of this protein was determined, compared between the tumors and correlated with clinicopathologic factors. ResultsStatistical analysis of lesions with a sufficient sample size showed significant differences in percentage and intensity between both epithelial and stromal components of all tumors (p<0.05). Pairwise-comparisons demonstrated significantly higher staining-percentage of epithelial cells (p=0.02) in Warthin’s tumor compared to pleomorphic adenoma and adenoid cystic carcinoma. Similarly, significantly higher staining intensities and/or percentages was observed in mucoepidermoid carcinoma and adenoid cystic carcinoma compared to pleomorphic adenoma and Warthin’s tumor (p<0.05). Of the clinicopathologic factors, there was only a significant negative correlation between stromal percentage of mucoepidermoid carcinoma and age and a significant difference between stromal intensity+percentage of adenoid cystic carcinoma and gender (p<0.05). ConclusionsAccording to our findings we postulate that stromal syndecan-1 correlates with the behavior of salivary gland tumors, with malignant neoplasms demonstrating a higher expression, indicating a role for syndecan-1 in invasion and metastasis.

SYNCHRONOUS EXPRESSION OF E-CADHERIN AND SYNDECAN-1 IN AMELOBLASTOMA: A PRELIMINARY STUDY

Objectives This study aimed to evaluate the percentage of expression and the possibility of synchronicity between E-cadherin (Ecad) and Epithelial syndecan-1 (Syn-1E) in Unicystic ameloblastoma (UAM) and solid multicystic ameloblastoma (SMA) and the association between this synchronicity and stromal immunoexpression of Syn1 (Syn1S). Findings Immunohistochemical analysis of Ecad and Syn1 was performed for 30 (15 UAM, 15 SMA) cases of ameloblastoma, the percentage of expression was evaluated with the average value for expression, and intensity was evaluated with the Immunomebrane plug-in. (Image J, BioMediTech, Finland) The percentage expression of Ecad and Syn1E was high in UAM. (p 0.05) Conclusions We observed synchronicity in the expression of Ecad and Syn1E in both types of ameloblastomas. The adhesiveness of the tumoral cells is probably related to the regulation of expression of both proteins; thus, an increase or reduction of synchronicity is related to cell invasion and the capacity to migration to the stroma, which was reflected in the behavior of the ameloblastomas in the present cases. This assumption may be further supported by an increase in expression of Syn1S in the SMAs; therefore, it is possible that the low synchronicity between Ecad and Syn1E constitute an important factor for the aggressiveness of ameloblastomas.

Differences in E-Cadherin and Syndecan-1 Expression in Different Types of Ameloblastomas.

Ameloblastomas are a group of benign, locally aggressive, recurrent tumors characterized by their slow and infiltrative growth. E-Cadherin and syndecan-1 are cell adhesion molecules related to the behavior of various tumors, including ameloblastomas. Ninety-nine ameloblastoma samples were studied; the expression of E-cadherin and syndecan-1 were evaluated by immunohistochemistry. E-Cadherin and epithelial syndecan-1 were more highly expressed in intraluminal/luminal unicystic ameloblastoma than in mural unicystic ameloblastoma and solid/multicystic ameloblastoma, whereas the stromal expression of syndecan-1 was higher in mural unicystic ameloblastoma and solid/multicystic ameloblastoma. Synchronicity was observed between E-cadherin and epithelial syndecan-1; the expression was correlated with intensity in all cases. There was a strong association between expression and tumor size and recurrence. The evaluation of the expression of E-cadherin and syndecan-1 are important for determining the potential aggressiveness of ameloblastoma variants. Future studies are required to understand how the expression of these markers is related to tumor aggressiveness.

Syndecan-1 expression is associated with tumor size and EGFR expression in colorectal carcinoma: a clinicopathological study of 230 cases.

Background: Syndecan-1 (SDC1) is reported to modulate several key processes of tumorigenesis and has variable expression in many cancers. To date, the cause of altered expression has not been elucidated. In this study, we compared SDC1 expression with various clinicopathological parameters and molecular markers to evaluate its clinical significance in colorectal carcinoma.Methods: We screened for SDC1 expression using immunohistochemistry in 230 surgical specimens of primary colorectal carcinoma from patients consecutively treated between 2008 and 2011 at Seoul St. Mary's Hospital, The Catholic University of Korea. The relationship between SDC1 expression and various clinicopathological parameters and molecular markers was analyzed.Results: The tumors were principally located in the left colon (71.3%) and rectum (33.5%). There were 216 (93.9%) adenocarcinomas, 10 (4.3%) mucinous adenocarcinomas, and 4 other tumors. Most of the carcinomas were pT3 (68.3%) and pT4 (22.2%). There was regional lymph node metastasis in 140 patients. SDC1 expression was identified in the cancer cells of 212 (96.8%) colon cancer cases. Of the SDC1-positive cases, 131 showed predominantly membranous immunopositivity, and 81 showed a predominantly cytoplasmic staining pattern. Mixed membranous and cytoplasmic staining was observed in 154 cases. In 93 cases, stromal SDC1 reactivity was noted. Epithelial SDC1 immunopositivity was significantly associated with tumor size (p = 0.016) and epidermal growth factor receptor expression (p = 0.006). However, it was not significantly correlated with lymph node metastasis, distant metastasis, lymphatic or vascular invasion, or KRAS mutation. In addition, stromal SDC1 immunopositivity was significantly associated with the male sex (p = 0.018).Conclusions: The expression profile of SDC1 may be of clinical value in colorectal cancer and may help in identifying aggressive forms of colorectal carcinoma. Further studies are needed in order to better understand the role of SDC1 in the progression and invasiveness of colorectal carcinoma.

Epithelial and stromal syndecan‐1 and ‐2 are distinctly expressed in oral‐ and cutaneous squamous cell carcinomas

Oral squamous cell carcinoma (OSCC) and cutaneous squamous cell carcinoma (CSCC) are epithelial neoplasms of which OSCC has worse survival and higher risk of metastasis than CSCC. The aim of this study was to explore the differences of immunoexpressions between syndecan-1 and -2 in OSCC and head and neck CSCC. A total of 35 patients diagnosed with OSCC and 25 with CSCC, presented T1 and T2 tumors and treated at Helsinki University Central Hospital between years 2001 and 2009, were selected into this study. The levels and locations of syndecan-1 and -2 immunostainings were analyzed using formalin-fixed and paraffin-embedded tissue samples of OSCC and CSCC cases together with clinical data. Cell membrane epithelial syndecan-1 expression decreased significantly compared to normal tissue in both cancer types. Cell membrane syndecan-1 expression in the invasive front had negative correlation with invasion depth of both tumors (OSCC, r = -0.339, P = 0.025; CSCC, r = -0.469, P = 0.004). In cancers over 4-mm invasion depth, the number of stromal syndecan-1-positive collagen fibers and inflammatory cells were higher in OSCC than in CSCC. Syndecan-2 expression in non-malignant stroma was higher in CSCC than in OSCC tumors. In addition, unlike syndecan-1, syndecan-2 was more often and more intensively expressed in the tumor inflammatory cells in CSCC than in OSCC. Our results suggest that variable stromal expression of syndecan-1 and -2 in OSCC compared to CSCC may at least partially explain the differences in their clinical behavior.

Tubular epithelial syndecan-1 maintains renal function in murine ischemia/reperfusion and human transplantation

Syndecan-1, a heparan sulfate proteoglycan, has an important role in wound healing by binding several growth factors and cytokines. As these processes are also crucial in damage and repair after renal transplantation, we examined syndecan-1 expression in human control kidney tissue, renal allograft protocol biopsies, renal allograft biopsies taken at indication, and non-transplant interstitial fibrosis. Syndecan-1 expression was increased in tubular epithelial cells in renal allograft biopsies compared with control. Increased epithelial syndecan-1 in allografts correlated with low proteinuria and serum creatinine, less interstitial inflammation, less tubular atrophy, and prolonged allograft survival. Knockdown of syndecan-1 in human tubular epithelial cells in vitro reduced cell proliferation. Selective binding of growth factors suggests that syndecan-1 may promote epithelial restoration. Bilateral renal ischemia/reperfusion in syndecan-1-deficient mice resulted in increased initial renal failure and tubular injury compared with wild-type mice. Macrophage and myofibroblast numbers, tubular damage, and plasma urea levels were increased, and tubular proliferation reduced in the kidneys of syndecan-1 deficient compared with wild-type mice 14 days following injury. Hence syndecan-1 promotes tubular survival and repair in murine ischemia/reperfusion injury and correlates with functional improvement in human renal allograft transplantation.

The Prognostic Value of Syndecan-1 in Ovarian Cancer Patients with Long-Term Follow up

IntroductionSyndecan-1 plays a role in the cell regulation through cell-extracellular matrix adhesion, cell-cell adhesion, migration, and morphogenesis. It functions as a co-receptor for several growth factors, modulating the affinity of the growth-factor receptor interactions. Syndecan-1 has been investigated as a prognostic factor for several malignant cancer types, but its role still seems unclear. The purpose of the present study was to investigate the possible role of syndecan-1 as a prognostic factor in ovarian cancer. MethodsThe expression of syndecan-1 was examined in ovarian cancer specimens from 164 patients who were enrolled in a Danish protocol after primary surgery in the period from 1991 to 1994. Immunohistochemistry and tissue microarrays (TMAs) were used for the detection of syndecan-1 in both tumor epithelial and stromal cells. ResultsThe median duration of follow-up for those still alive was 18 years. Positive tumor epithelial syndecan-1 staining was found in 18% of the patients, whereas positive stromal syndecan-1 immunoreactivity was seen in 50% of the patients. Positive expression of syndecan-1 in epithelial cells was observed less frequently in serous adenocarcinoma, whereas positive stromal expression was found more frequently in poorly differentiated tumors. Positive epithelial syndecan-1 expression was associated with unfavorable overall survival (OS) in univariate analysis (P = 0.02), which, however, was not confirmed in multivariate analysis, although there was a tendency (P = 0.12) and a hazard ratio of 1.52. ConclusionSyndecan-1 is present in a subset of ovarian carcinomas and may be an indicator of survival, but further investigations are required.

Clinical significance of syndecan-1 and versican expression in human epithelial ovarian cancer

Proteoglycans are ubiquitous components of the extracellular matrix and cell surface, and may mediate tumor progression and metastasis. The aim of this study was to evaluate the expression of syndecan-1 and versican in epithelial ovarian cancer. We immunohistochemically evaluated the expression of syndecan-1 and versican in 111 patients with epithelial ovarian cancer, and analyzed the correlation of this expression with various observed clinicopathological features, including patient outcome. There is a significant correlation between primary and metastatic sites with respect to syndecan-1 and versican expression. Epithelial syndecan-1 expression was significantly lower in patients with advanced disease. Epithelial versican expression was significantly higher in patients with early disease, especially in clear cell adenocarcinoma patients. Stromal syndecan-1 and versican expression was significantly higher in patients with advanced disease. Multivariate analysis showed that negative epithelial syndecan-1 expression was an independent prognostic factor for progression-free survival. Stromal syndecan-1 and versican co-expression was of borderline significance for progression-free and overall survival. Loss of epithelial syndecan-1 expression and induction of stromal syndecan-1 and versican expression may be associated with tumor progression in epithelial ovarian cancer. Syndecan-1 and versican expression status can serve as an indicator of prognosis in patients with epithelial ovarian cancer.

Reduction of syndecan‐1 expression during lip carcinogenesis

Actinic cheilitis (AC) is an oral pre-cancerous lesion that sometimes develops into lip squamous cell carcinoma (SCC). Syndecan-1, a transmembrane heparan sulfate proteoglycan, modulates cell-proliferation, adhesion, migration and angiogenesis. Malignant epithelial cells often down-regulate their own syndecan-1 production, and are capable of inducing aberrant syndecan-1 expression in stromal cells. The aim of this study was to evaluate the variations in syndecan-1 expression during lip carcinogenesis, in normal lip (NL), AC and well-differentiated lip SCC. Biopsies of NL vermillion (n = 19), AC (n = 23) and lip SCC (n = 24) were stained immunohistochemically for syndecan-1. Syndecan-1 expression was significantly reduced in AC and lip SCC as compared to NL (P < 0.05), with a significant reduction in lip SCC as compared to AC (P < 0.0001). In lip SCC lesions, syndecan-1 expression at the epithelium overlying the tumor was increased when compared to the tumor itself (P < 0.03), but was significantly reduced as compared to AC and NL (P < 0.001). The results showed that epithelial syndecan-1 expression is reduced as lip carcinogenesis progresses (NL>AC>lip SCC), suggesting that syndecan-1 could be a useful marker of malignant transformation in the lip.

Reduced production of sulfated glycosaminoglycans occurs in Zambian children with kwashiorkor but not marasmus

Background:Kwashiorkor, a form of severe malnutrition with high mortality, is characterized by edema and systemic abnormalities. Although extremely common, its pathophysiology remains poorly understood, and its characteristic physical signs are unexplained.Objective: Because kwashiorkor can develop in protein-losing enteropathy, which is caused by a loss of enterocyte heparan sulfate proteoglycan (HSPG), and previous observations suggest abnormal sulfated glycosaminoglycan (GAG) metabolism, we examined whether intestinal GAG and HSPG are abnormal in children with kwashiorkor.Design: Duodenal biopsy samples collected from Zambian children with marasmus (n = 18), marasmic kwashiorkor (n = 8), and kwashiorkor (n = 15) were examined for expression of HSPG, GAGs, and immunologic markers and compared against reference samples from healthy UK control children. GAG and HSPG expression density and inflammatory cell populations were quantitated by computerized analysis.Results: The kwashiorkor group was less wasted and had a lower HIV incidence than did the other groups. All duodenal biopsy samples showed inflammation compared with the histologically uninflamed control samples. Biopsy samples from marasmic children had greater inflammation and greater CD3+ and HLA-DR (human leukocyte antigen DR)–positive cell densities than did samples from children with kwashiorkor. Expression of both HSPG and GAGs was similar between marasmic and well-nourished UK children but was markedly lower in children with kwashiorkor in both the epithelium and lamina propria. Although underglycosylated and undersulfated, epithelial syndecan-1 protein was normally expressed in kwashiorkor, which confirmed that abnormalities arise after core protein synthesis.Conclusions: Intestinal HSPG loss occurs in kwashiorkor, which may precipitate protein-losing enteropathy to cause edema. If occurring systemically, impaired HSPG expression could cause several previously unexplained features of kwashiorkor. We speculate that a genetic predisposition to reduced HSPG biosynthesis may offer a contrasting selective advantage, by both diminishing protein catabolism during transient undernutrition and protecting against specific infectious diseases.

Association of loss of epithelial syndecan-1 with stage and local metastasis of colorectal adenocarcinomas: An immunohistochemical study of clinically annotated tumors

BackgroundSyndecan-1 is a transmembrane proteoglycan with important roles in cell-cell and cell-extracellular matrix adhesion and as a growth factor co-receptor. Syndecan-1 is highly expressed by normal epithelial cells and loss of expression has been associated with epithelial-mesenchymal transition and the transformed phenotype. Loss of epithelial syndecan-1 has been reported in human colorectal adenocarcinomas, but whether this has prognostic significance remains undecided. Here we have examined syndecan-1 expression and its potential prognostic value with reference to a clinically annotated tissue microarray for human colon adenocarcinomas.MethodsSyndecan-1 expression was examined by immunohistochemistry of a tissue microarray containing cores from 158 colorectal adenocarcinomas and 15 adenomas linked to a Cleveland Clinic, IRB-approved database with a mean clinical follow-up of 38 months. The Kaplan-Meier method was used to analyze the relationship between syndecan-1 expression and patient survival. Potential correlations between syndecan-1 expression and the candidate prognostic biomarker fascin were examined.ResultsSyndecan-1 is expressed at the basolateral borders of normal colonic epithelial cells. On adenocarcinoma cells, syndecan-1 was present around cell membranes and in cytoplasm. In 87% of adenocarcinomas, syndecan-1 was decreased or absent; only 13% of patients had stained for syndecan-1 on more than 75% of tumor cells. Decreased syndecan-1 correlated with a higher TNM stage and lymph node metastasis and was more common in males (p = 0.042), but was not associated with age, tumor location or Ki67 index. Reduced tumor syndecan-1 staining also correlated with upregulation of stromal fascin (p = 0.016). Stromal syndecan-1 was observed in 16.6% of tumors. There was no difference in survival between patients with low or high levels of either tumor or stromal syndecan-1.ConclusionSyndecan-1 immunoreactivity was decreased in the majority of human colon adenocarcinomas in correlation with TNM stage and metastasis to local lymph nodes. In a small fraction of adenocarcinomas, syndecan-1 was upregulated in the local stroma. Syndecan-1 expression status did not correlate with patient survival outcomes. Combined analysis of syndecan-1 in relation to a potential prognostic biomarker, fascin, identified that loss of tumor syndecan-1 correlated significantly with strong stromal fascin staining.

Syndecan-1 Expression in Gallbladder Cancer and Its Prognostic Significance

Aim: To determine whether the immunohistochemical detection of syndecan-1 could provide useful information as a novel therapeutic or prognostic factor in primary gallbladder (GB) cancer. Materials and Methods: Forty-three GB cancer tissues were evaluated by immunohistochemistry for syndecan-1 expression. The relationship between syndecan-1 expression and clinicopathological characteristics, and the univariate survival analysis for the influence of the syndecan-1 expression on the overall survival were analysed. Results: Epithelial syndecan-1 immunoreactivity was observed in 25 (58.1%) of the 43 GB cancer cases. The tumors with a positive syndecan-1 expression more frequently showed lymph node metastasis (p = 0.037). Although there was no statistically significant association, the tumors with a positive syndecan-1 expression tended to show a deeper invasion depth (p = 0.087) and more frequent lymphovascular invasion (p = 0.064). The Kaplan-Meier survival curves demonstrated that patients with positive syndecan-1 expression had a significantly shorter survival time than those patients with negative syndecan-1 expression (p = 0.05). Conclusions: A subset of GB cancers revealed an epithelial overexpression of syndecan-1, which was associated with a progressive pathological feature and an aggressive clinical course. Therefore, epithelial syndecan-1 expression may be a predictor for a poor prognosis in patients with GB cancer.

Prognostic impact of syndecan-1 expression in invasive ductal breast carcinomas

Carcinoma cells lack syndecan-1 expression when they are transiting from an epithelial to a less-differentiated mesenchymal phenotype (epithelial–mesenchymal transition, EMT). Furthermore, a shift of syndecan-1 expression from malignant epithelial cells to reactive stromal cells has also been observed during progression of many carcinomas. Finally, epithelial and/or stromal syndecan-1 expression is of prognostic value in many carcinomas. Because recent results are contradictory in breast carcinomas, we have re-evaluated the prognostic significance of syndecan-1 expression in a cohort of 80 patients with invasive ductal breast carcinomas. The tumours from 80 patients diagnosed with invasive ductal breast carcinomas were used to construct a tissue microarray, which was stained with syndecan-1 by immunohistochemistry. We correlated syndecan-1 expression with clinicopathologic parameters and relapse-free survival (RFS). Exclusive epithelial expression of syndecan-1 is observed in 61.25% of the patients, whereas exclusive stromal expression is observed in 30% of the patients. Only 8.75% of the patients had both stromal and epithelial expressions of syndecan-1. A significant correlation was found between the loss of syndecan-1 epithelial expression and the syndecan-1 stromal expression with high grade of malignancy (P=0.011). The loss of syndecan-1 epithelial expression is correlated with RFS (P=0.001). Using multivariate Cox analysis, loss of epithelial syndecan-1 expression was the only prognostic indicator (P<0.001). We concluded that the loss of syndecan-1 epithelial expression was of strong prognostic value in breast carcinomas.

Acceleration of epithelial cell syndecan-1 shedding by anthrax hemolytic virulence factors.

BackgroundIt has been recently reported that major pathogens Staphylococcus aureus and Pseudomonas aeruginosa accelerate a normal process of cell surface syndecan-1 (Synd1) ectodomain shedding as a mechanism of host damage due to the production of shedding-inducing virulence factors. We tested if acceleration of Synd1 shedding takes place in vitro upon treatment of epithelial cells with B. anthracis hemolysins, as well as in vivo during anthrax infection in mice.ResultsThe isolated anthrax hemolytic proteins AnlB (sphingomyelinase) and AnlO (cholesterol-binding pore-forming factor), as well as ClnA (B. cereus homolog of B. anthracis phosphatidyl choline-preferring phospholipase C) cause accelerated shedding of Synd1 and E-cadherin from epithelial cells and compromise epithelial barrier integrity within a few hours. In comparison with hemolysins in a similar range of concentrations, anthrax lethal toxin (LT) also accelerates shedding albeit at slower rate. Individual components of LT, lethal factor and protective antigen are inactive with regard to shedding. Inhibition experiments favor a hypothesis that activities of tested bacterial shedding inducers converge on the stimulation of cytoplasmic tyrosine kinases of the Syk family, ultimately leading to activation of cellular sheddase. Both LT and AnlO modulate ERK1/2 and p38 MAPK signaling pathways, while JNK pathway seems to be irrelevant to accelerated shedding. Accelerated shedding of Synd1 also takes place in DBA/2 mice challenged with Bacillus anthracis (Sterne) spores. Elevated levels of shed ectodomain are readily detectable in circulation after 24 h.ConclusionThe concerted acceleration of shedding by several virulence factors could represent a new pathogenic mechanism contributing to disruption of epithelial or endothelial integrity, hemorrhage, edema and abnormal cell signaling during anthrax infection.

Differential Immunohistochemical Expression of Syndecan-1 and Tumor Necrosis Factor Alpha in Colonic Mucosa of Patients with Crohn’s Disease

Tumor necrosis factor alpha (TNFα) in intestinal mucosa plays a key role in the inflammation characterizing Crohn’s disease (CD). Moreover, adhesion molecule syndecan-1 mediates the maintenance of mucosal integrity and supports tissue repair. Therefore, our aim in this study was to correlate simultaneous expression of TNFα and syndecan-1 in patients affected by CD. Biopsies from 10 patients with CD of large bowel and 10 subjects with irritable bowel syndrome (controls) were studied by immunohistochemical detection of both TNFα and syndecan-1 on successive serial sections. Overall labeling index (OLI) was indicated by the percentage of positive stromal (i.e., nonepithelial) cells/1000 counted in randomized fields, whereas selected labeling index (SLI) was represented by the simultaneous evaluation of both molecules in a same single selected field of each specimen. TNFα and syndecan-1 OLI were significantly higher in CD compared with controls, while SLI showed an inverse relationship between the molecules in CD which was not observed in controls. Epithelial syndecan-1 cytoplasmatic staining of superficial epithelium was associated with loss of basolateral staining in the crypts and high stromal TNFα in CD. In conclusion, TNFα and syndecan-1 expression is increased in the intestinal mucosa of patients with CD. However, the expression of the two molecules is inversely related when a single field is considered, these data supporting the possibility of a downregulation exerted by TNFα.

Differential Immunohistochemical Expression of Syndecan-1 and Tumor Necrosis Factor Alpha in Colonic Mucosa of Patients with Crohn’s Disease

Tumor necrosis factor alpha (TNFα) in intestinal mucosa plays a key role in the inflammation characterizing Crohn’s disease (CD). Moreover, adhesion molecule syndecan-1 mediates the maintenance of mucosal integrity and supports tissue repair. Therefore, our aim in this study was to correlate simultaneous expression of TNFα and syndecan-1 in patients affected by CD. Biopsies from 10 patients with CD of large bowel and 10 subjects with irritable bowel syndrome (controls) were studied by immunohistochemical detection of both TNFα and syndecan-1 on successive serial sections. Overall labeling index (OLI) was indicated by the percentage of positive stromal (i.e., nonepithelial) cells/1000 counted in randomized fields, whereas selected labeling index (SLI) was represented by the simultaneous evaluation of both molecules in a same single selected field of each specimen. TNFα and syndecan-1 OLI were significantly higher in CD compared with controls, while SLI showed an inverse relationship between the molecules in CD which was not observed in controls. Epithelial syndecan-1 cytoplasmatic staining of superficial epithelium was associated with loss of basolateral staining in the crypts and high stromal TNFα in CD. In conclusion, TNFα and syndecan-1 expression is increased in the intestinal mucosa of patients with CD. However, the expression of the two molecules is inversely related when a single field is considered, these data supporting the possibility of a downregulation exerted by TNFα.

Epithelial Syndecan-1 Expression Is Associated with Stage and Grade in Colorectal Cancer

Objectives: Loss of epithelial heparan sulfate proteoglycan syndecan-1 has been associated with a more aggressive behavior in various cancer forms, but the prognostic significance of syndecan-1 expression in colorectal cancer is unclear. The aim of this study was to evaluate the prognostic value of immunohistochemical syndecan-1 expression in a series of 237 patients with colorectal cancer. Methods: Paraffin-embedded formalin-fixed specimens were stained with a syndecan-1-specific monoclonal antibody, and both the epithelial and stromal expression were analyzed. Results: Epithelial expression of syndecan-1 was seen in 222 tumors (94%), and it was associated with low stage of disease (p = 0.002) and low histological differentiation grade (p = 0.048). The cumulative 5-year survival of patients with weak and strong syndecan-1 expression was 49 and 54 %, respectively (p = 0.234). Syndecan-1 stromal immunoreactivity was observed in 138 tumors (58%), but lacked prognostic significance. Staining pattern and distribution can be viewed from digitized representative microscope slides (virtual slides) at http://www.webmicroscope.net/supplements/syndecan. Conclusions: The results are in line with previous reports in that low epithelial syndecan-1 expression was associated with a higher histological grade and a more advanced clinical stage of the patients. This study shows that syndecan-1 is expressed also in stromal tissue of colorectal cancer, but it does not support the proposed role of stromal syndecan-1 expression as a marker of poor clinical outcome.

Prognostic significance of syndecan-1 expression in human endometrial cancer

Background:: Syndecan-1 binds to various extracellular matrix components via its heparan sulfate glycosaminoglycans. The aim of this study was to investigate syndecan-1 expression in endometrial cancers.Patients and methods:: We investigated the expression of the syndecan-1 core protein by immunohistochemistry in 109 endometrial cancers, and analyzed correlation with various clinicopathological features, including patient outcome.Results:: Epithelial syndecan-1 expression was significantly lower in advanced stage, high grade, deep myometrial invasion, cervical involvement, lymph node metastasis, lymph vascular space involvement and positive peritoneal cytology. Stromal syndecan-1 expression was significantly higher in high-grade tumors. The disease-free and overall survival rates of patients exhibiting both low epithelial and high stromal syndecan-1 expression was poor. Multivariate analysis showed that high stromal syndecan-1 expression was an independent prognostic factor for both disease-free and overall survival. Low epithelial syndecan-1 expression was a prognostic factor only in the univariate analysis.Conclusions:: Loss of epithelial syndecan-1 and induction of stromal syndecan-1 expression may be associated with tumor progression. Stromal syndecan-1 expression can serve as an indicator of poor prognosis in patients with endometrial cancer.

Plasmacytoid transitional cell carcinoma of the urinary bladder

A case of rare plasmacytoid transitional cell carcinoma of the urinary bladder in a 60-year old man is described. The presence of end-stage disease did not allow for any efficacious therapy. Immunohistochemistry showed the tumor cells to be reactive for epithelial markers and syndecan-1 (CD138).