FR-P-104 Histopathological evaluation of the iron content in liver biopsies J . Kelterborn 1 , K . Zöller 1 , J . Biet 1 , Y . Chen 1 , A . Herrmann 2 , M . Kiehntopf 3 , A . Stallmach 4 , I . Petersen 1 1 Friedrich-Schiller-University of Jena, Institute of Pathology, Jena, 2 Friedrich- Schiller-University of Jena, Institute of Internal Medicine, Jena, 3 Friedrich- Schiller-University of Jena, Institute of Clinical Chemistry, Jena, 4 Friedrich- Schiller-University of Jena, Institute for Internal Medicine, Jena Aims. Hereditary hemochromatosis is the most common autosomal recessive genetic disease in Northern Europe. Iron overload leads to serious damage of various organ systems. Early diagnosis is desirable due to the possibility of prevention of severe organ dysfunction. However, the majority of patients are diagnosed in adulthood in the context of an uncertain liver pathology. Liver biopsy is an essential tool of analysis. In the present work two new iron scores were tested for their validity in the diagnosis of hemochromatosis. Methods. At the Institute for Pathology of the University Hospital of Jena all liver samples of a 2-year period were retrieved from the pathology files and reviewed. In total, 2326 cases were assessed of which 60 were selected for an in-depth study on iron content. The mean age of the patients was 59 years, 72% originated from male patients. In all 60 samples a mutation analysis of the two most common gene loci in hemochromatosis were performed, i.e. HFE282 and HFE63. Moreover, using the clinical diagnosis documentation system, laboratory values of liver diseases and iron storage diseases were analyzed. The assessment of the iron content of the liver biopsies were done by the Prussian blue stain applying two scores with comprised a published 21-tier and a newly developed 5-tier grading system. Results. It was shown that both iron scores were highly correlated with each other (p
Abstracts FR-P-107 Comprehensive histological characterization of murine hepatocellular tumors – towards a classification of murine and human hepatocellular carcinomas L . Frick 1 , F . Böhm 2 , Y . Boege 1 , J . Friemel 2 , M . Heikenwael<strong>der</strong> 3 , A . Weber 2 1 University Zurich, Department of Pathology, Zürich, Switzerland, 2 University Zurich, Institute of Surgical Pathology, Zürich, Switzerland, 3 Munich, Institute for Virology and Helmholtz Zentrum, München Aims. The aim of our study is to characterise and compare different mouse models of hepatocellular carcinoma (HCC) which may reflect different ways of hepatocarcinogenesis in humans (including viral and toxic) in or<strong>der</strong> to test their applicability to human HCC. Methods. We have implemented high-throughput, high-quality scanning technology to make digital copies of all our histological slides. A viewing software is used to display sequential sections side-by-side on a computer screen, and to measure tumours and annotate them for later reference. This enables us to determine the morphological and immunohistochemical characteristics of each individual lesion efficiently and comprehensively, even if there are many tumours and dysplastic lesions per slide, and thus discover correlations that may otherwise have been missed. Results. We have found clear differences among the mouse models, not only in the un<strong>der</strong>lying liver pathology, but also in the spectrum of liver tumours that arises. In addition, certain regularities and correlations of tumour morphology and immunophenotype suggest a possible classification of liver tumours in mice. Using tissue microarrays of human HCC, we have discovered that the classification of murine tumours has cross-species applicability to human tumours. Conclusions. The results of our morphological and immunophenotypic studies, together with the data from molecular analyses, provide the basis for a classification of liver tumours that applies to both mice and humans. We also intend to show which mouse models recapitulate which aspects of hepatocarcinogenesis in humans, and may thus provide suitable models for testing therapeutic interventions. FR-P-108 LGR5 is differentially expressed in hepato-gastrointestinal tumors E . Simon1 , D . Petke1 , C . Böger1 , V . Warneke1 , H .-M . Behrens1 , C . Röcken1 1Christian-Albrechts-University, Institute of Pathology, Kiel Aims. Carcinomas of the hepato-gastrointestinal tract are still leading cause of cancer related deaths worldwide. The orphan G-protein-coupled receptor (GPCR) and Wnt-target protein LGR5 was recently identified as a stem cell marker for cells with intestinal differentiation. In this study we generated a polyclonal anti-LGR5 antibody to investigate protein expression in various hepato-gastrointestinal carcinomas and its correlation with clinicopathological patient characteristics. Methods. Differential expression of LGR5 was studied on transcriptional (real time-polymerase chain reaction) and translational level (immunohistochemistry) in carcinomas and corresponding normal mucosal specimens comprising seven different primary tumor sites, i.e. oesophagus, pancreas, stomach, liver, colon and rectum. The putative clinicopathological relevance of LGR5 expression in terms of patient survival and the histoanatomical distribution of the protein was studied in 100 patients with gastric carcinoma. Results. We succeeded to establish and characterize a highly specific antibody that recognizes the C-terminal tail of LGR5. LGR5 was differentially expressed on transcriptional and translational level in adenocarcinomas of the oesophagus, pancreas, stomach, colon, rectum, hepatocellular and cholangiocellular carcinoma of the liver compared with the adjacent non-neoplastic tissue. However, in intestinal type gastric cancer the localization and number of LGR5+ cells changed during tumorigenesis. 118 | Der Pathologe · Supplement 1 · 2012 Conclusions. Our results substantiate the significance of LGR5 on the biology of hepatogastrointestinal carcinomas and provide evidence for its function as potential stem cell marker and candidate therapeutic target in the stomach. The strikingly changed histoanatomical distribution of LGR5+ cells during tumorigenesis could be an important observation in un<strong>der</strong>standing tumor formation and progression. With our anti-LGR5 antibody we now have a useful tool for detection and further analyzes of LGR5 biological function. FR-P-109 Gene expression analysis of the Mcl-1delHEP mouse model of hepatocarcinogenesis reveals overlapping expression profiles with human hepatocellular carcinoma F . Böhm1 , Y . Böge2 , R . Maire2 , J . Friemel1 , M . Heikenwäl<strong>der</strong>3 , A . Weber1 1University Hospital Zurich, Institute of Surgical Pathology, Zürich, Switzerland, 2University Hospital Zurich, Institute of Neuropathology, Zürich, Switzerland, 3Institute of Virology, Helmholtz Center, Munich Aims. Apoptosis is regulated by a counterbalancing network of proapoptotic and pro-survival proteins. Mcl-1 is a crucial pro-survival factor, preventing cells to un<strong>der</strong>go apoptosis. Many chronic liver diseases are characterized by a constant loss of hepatocytes. Recently, we have shown that a mouse model with hepatocyte-specific deletion of Mcl-1 (Mcl-1delhep) reveals increased apoptosis, regeneration, and development of hepatocellular carcinomas (HCC). To better characterize apoptosis-driving tumorigenesis, we analyse gene expression patterns in the Mcl-1delhep model, and compare these to gene expression patterns in human liver tissues including HCC. Methods. RNA from livers of Mcl-1delhep mice, several other genetic mouse models and human HCCs of various etiologies were isolated, analysed and compared by quantitative real-time PCR. Results. RNA microarray of livers at 2 months of age uncovered significantly up- and downregulated genes in Mcl-1delhep mice compared to wild-type mice. Expression of Top 5 genes was also found to be significantly upregulated in 12 months old Mcl-1delhep mice (non-tumor and tumor tissue) and HCCs of various genetic mouse models for hepatocarcinogenesis as well as in human liver RNA from HCCs with different etiology. Conclusions. The Mcl-1delhep mouse model shows that increased apoptosis might serve as a main trigger of tumorigenesis, and thus recapitulates the human pathogenesis of chronic liver diseases such as liver tissue destruction and subsequent cancer formation. Overlapping gene expression patterns in the Mcl-1delhep mouse model, human tissues of chronic liver diseases and HCC confirms that the Mcl-1delhep mouse model is a valuable tool for studying human hepatocarcinogenesis, and thus also might be suitable for the identification of new molecular targets and interventional studies. FR-P-110 Clear cell foci of altered hepatocytes in human liver show an overexpression of the AKT/mTOR and Ras/Raf1 pathways as well as the lipogenic phenotype (similar to hepatocarcinogenesis in the rat and to human hepatocellular carcinoma) S . Ribback1 , D .F . Calvisi1 , C .-D . Heidecke2 , M . Birth3 , F . Dombrowski1 1 2 Universitätsmedizin Greifswald, Institut <strong>für</strong> <strong>Pathologie</strong>, Greifswald, Universitätsmedizin Greifswald, Klinik und Poliklinik <strong>für</strong> Chirurgie, Greifswald, 3Hanse-Klinikum Stralsund, Klinik <strong>für</strong> Allgemein-, Viszeral-, Thorax- und Gefäßchirurgie, Stralsund Aims. AKT/mTOR and Ras/Raf1 pathways as well as the lipogenic phenotype have been shown to be activated in a model of hepatocarcinogenesis in the rat induced by hyperinsulinemia and in human hepatocellular carcinomas. In the rat model the activation of these pathways starts
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Inhalt Der Pathologe · Supplement
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Inhalt Der Pathologe · Supplement
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Editorial Liebe Kolleginnen und Kol
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Kolorektales Karzinom 2 VO-005 Tran
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Keynote Lecture VO-014 Genetic dete
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(AMACR, FASN, GOLM1, GSP-pi, ERG) t
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to assess the correct rate of R1 re
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DNA damage, and cytotoxic drugs. Au
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HCV-positive formalin-fixed and par
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well as MET activation were examine
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or BRAF mutation, c-MYC and SIRT1 e
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AG Pneumopathologie III DO-032 Remo
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immature granulopoiesis showed a st
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ned, if well-defined mantle zones,
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phomas). Most prominent gains or am
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DO-062 Tumor-associated macrophages
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DO-080 DOG1: an immunohistochemical
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AG Oralpathologie DO-087 Detection
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DO-094 Do activated fibroblasts inf
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DO-101 Histopathological analysis o
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DO-108 Identification of potential
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Conclusions. In conclusion, 454 par
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subgroup of patients with B-Raf mut
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DO-002b Impact of terminologies in
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Methods. We performed MCPyV-FISH of
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FR-013 HPV-genotype distribution in
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Methods. Three different techniques
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(i.e. investment in equipment and e
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FR-032 COLD-PCR: a powerful tool in
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dissection (MBLND) technique to imp
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SO-005 Prevalence of mutations in s
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SO-011 Methylation profiling and in
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more effective than SAHA alone and
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- Page 132 and 133: FR-P-149 Combination of Castleman d
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Results. The papillary RCC type II
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SA-P-098 Male infertility: assessme
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SA-P-104 Process oriented scientifi
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Conclusions. The IBDW offers a uniq
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L Lasitschka F. DO-046 Lehmann A. F