EpCAM expression in primary tumour tissues and metastases: an immunohistochemical analysis

Epithelial cell adhesion molecule (EpCAM) is a cell surface protein with oncogenic features that is expressed on healthy human epithelia and corresponding malignant tumours. EpCAM expression frequently correlates with more aggressive tumour behaviour and new EpCAM-specific therapeutic agents have recently been approved for clinical use in patients with cancer. However, no consensus exists on how and when to evaluate EpCAM expression in patients with cancer

Effects of EpCAM overexpression on human breast cancer cell lines

<p>Abstract</p> <p>Background</p> <p>Recently, EpCAM has attracted major interest as a target for antibody- and vaccine-based cancer immunotherapies. In breast cancer, the EpCAM antigen is overexpressed in 30-40% of all cases and this increased expression correlates with poor prognosis. The use of EpCAM-specific monoclonal antibodies is a promising treatment approach in these patients.</p> <p>Methods</p> <p>In order to explore molecular changes following EpCAM overexpression, we investigated changes of the transcriptome upon EpCAM gene expression in commercially available human breast cancer cells lines Hs578T and MDA-MB-231. To assess cell proliferation, a tetrazolium salt based assay was performed. A TCF/LEF Reporter Kit was used to measure the transcriptional activity of the Wnt/β-catenin pathway. To evaluate the accumulation of β-catenin in the nucleus, a subcellular fractionation assay was performed.</p> <p>Results</p> <p>For the first time we could show that expression profiling data of EpCAM transfected cell lines Hs578T^EpCAMand MDA-MB-231^EpCAMindicate an association of EpCAM overexpression with the downregulation of the Wnt signaling inhibitors SFRP1 and TCF7L2. Confirmation of increased Wnt signaling was provided by a TCF/LEF reporter kit and by the finding of the nuclear accumulation of ß-catenin for MDA-MB-231^EpCAMbut not Hs578T^EpCAMcells. In Hs578T cells, an increase of proliferation and chemosensitivity to Docetaxel was associated with EpCAM overexpression.</p> <p>Conclusions</p> <p>These data show a cell type dependent modification of Wnt signaling components after EpCAM overexpression in breast cancer cell lines, which results in marginal functional changes. Further investigations on the interaction of EpCAM with SFRP1 and TCF7L2 and on additional factors, which may be causal for changes upon EpCAM overexpression, will help to characterize unique molecular properties of EpCAM-positive breast cancer cells.</p

Hodgkin lymphoma in Tyrol-a population-based study

We aimed to analyze the epidemiology, clinical characteristics, and outcome of patients with Hodgkin lymphoma (HL) diagnosed in Tyrol. All patients with newly diagnosed HL between 1993 and 2005 were included in this study. Among the 158 cases included, nodular lymphocytic predominant HL (nodular paragranuloma) was identified in ten cases (6%) whereas the majority of patients had classical Hodgkin lymphoma. Age (p > 0.01), sex (p = 0.03), risk groups according to the German Hodgkin Study Group stratification (p > 0.01), and bone marrow infiltration (p > 0.01) were of prognostic significance considering overall survival (OS) whereas histological subtype and bulky disease were not. The 5- and 10-year OS rates for the total group were 89% and 85%, respectively. Notably, in patients with advanced-stage HL (n = 49), combined modality treatment resulted in significantly better OS than chemotherapy alone (p = 0.01). Three patients developed a second hematological malignancy and one patient developed breast cancer. However, five patients (3%) had a malignant hematological disorder before occurrence of HL. Concerning treatment-related toxicity, bleomycin-associated lung toxicity was observed in six (4%) patients and five (3%) developed lethal treatment-related infectious complications. Our results provide evidence that the incidence rate of HL in Tyrol is comparable to other Western countries. Modern risk-adapted treatment results in excellent long-term prognosis but may be complicated by serious nonhematological side effects, in particular, infections and bleomycin-induced lung toxicity. Furthermore, 3% of HL patients had an antecedent malignant hematological disease before occurrence of HL