96. Jahrestagung der Deutschen Gesellschaft für Pathologie e. V ...

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in the context of therapy response before. Immunohistochemistry of the mitochondrial protein COX7A2 in the validation set confirmed the MALDI Imaging results and revealed the predictive impact of COX7A2 (p=0.0015). By electron microscopy we found, that the loss of these proteins is strongly associated with a severe mitochondrial damage. Conclusions. MALDI Imaging is able to detect novel proteomic patterns distinguishing responders from non-responders. These protein patterns provide new insights in mechanisms of response. For the first time we could show that mitochondrial dysfunction is a predisposition for response to neoadjuvant chemotherapy in Barrett’s cancer. FR-P-043 Heterogeneity of TP53 mutations in gastric adenocarcinomas as well as their corresponding lymph node metastases D . Mones1 , G . Cadeddu1 , K .-L . Schäfer1 , H .E . Gabbert1 , S .E . Baldus1 1University of Düsseldorf, Institute of Pathology, Düsseldorf Aims. The frequency of TP53 mutations in gastric adenocarcinomas as well as the prognostic and predictive value of this biomarker is still controversially discussed. In order to elucidate if genetic mosaicism may explain at least in part the conflicting results obtained in previous studies, we investigated the intratumoral heterogeneity of TP53 mutations analysing tissue specimens from tumor center, invasion front and lymphonodal metastases. Methods. We studied a series of 75 gastric adenocarcinomas comprising 25 diffuse type, 24 intestinal type and 26 mixed type carcinomas according to Laurén. DNA of the paraffin-embedded tissue samples from tumor center and invasion front (n=75) as well as corresponding lymph node metastases (n=47) was obtained by microscopically controlled manual microdissection. DNA was purified and subjected to PCR amplification of TP53 exon 5–8 followed by direct sequencing. Results. TP53 mutations were observed in 34 of the 75 primary tumors (45%). Intratumoral heterogeneity of TP53 mutations was found in 13 primary tumors (17%): Two samples showed the mutation only in the invasion front, ten cases only in the tumor center and one case showed different mutations in invasion front and tumor center. There was no significant difference between the mutation rates in diffuse type (40%) compared to intestinal type adenocarcinomas (50%), while mixed type carcinomas showed a mutation in 46% of the cases. In addition, there was no difference between pT1/pT2 tumors (46%) and pT3/pT4 tumors (45%). Mutations in the lymph node metastases were found in 19 of 47 specimens (40%). Genetic heterogeneity between primary tumor and lymph node metastases was observed in 12 of the 47 cases (26%) comprising six cases showing the TP53 mutation only in the primary tumor, but not in the lymph node metastasis as well as four cases exhibiting a mutation in the lymph node metastasis, but not in the primary tumor. In two cases different mutations in primary tumor and corresponding lymph node metastasis were observed. Conclusions. Intratumoral heterogeneity of TP53 mutations is present in 17% of gastric adenocarcinomas and may therefore contribute to the controversial results regarding the prognostic value of the TP53 status. In addition, in 26% of the cases heterogeneity between TP53 mutations in primary tumors and lymph node metastases was observed. This should be considered in future studies on the predictive and prognostic value of TP53 mutation analysis in gastric adenocarcinomas. FR-P-044 Gastric Polyvinylpyrrolidon (PVP) Athrozytosis in chronic hemodialysed patients S .A . Thies1 , B . Kaduk2 , R . Ott3 , S . Turi4 , M . Sarbia5 1University of Zurich, Institute of Surgical Pathology, Zürich, Switzerland, 2 3 Kaduk Medical Service (KMS) GmbH, Baar, Switzerland, Gastroenterologie Bogenhausen, Gemeinschaftspraxis Dr . Schatke, Munich, 4Medizentrum Erlangen, Gemeinschaftspraxis Internist/Gastroenterologie, Erlangen, 5Pathologie München Nord, Munich Aims. The originally as plasma expander developed and applied high molecular Polyvinylpyrrolidone (PVP) – a polymer of the monomer N-Vinylpyrrolidon cannot be eliminated by diuresis nor metabolised by liver. These PVP polymers were phagocytosed by macrophages and permanently arrested. According to the type and topos of application of PVP – intradermal, subcutaneous, intracavitary, intraperitoneal, interpleural or intravenous – the phenotype of this storage disease differs and is predictive. The only non-predictive manifestation and severity of the accumulation and conditio sine qua non is due to the entrance of the high molecular PVP polymers into the blood circulation. This induces a high risk situation for the patients. For that reason high molecular PVP is not yet used as plasma expander. But nevertheless there is an ubiquitary (generalised) PVP-thesaurismosis, e.g. using PVP-coating fibre filters in human hemodialysis. Methods. We examined gastric biopsies of two patients with chronic hemodialysis in history without defined clinical question. The main histological topic was aggregates of isolated or grouped large macrophages with a certain but non-characteristic staining pattern (indirect indicators for PVP; i.e. advice): – H&E: intracytoplasmic blue-gray globules – Sirius red: brightly red deposits on a pale yellow background – Argentic impregnation: markedly coloured dark black deposits – PAS: negative – v. Kossa: negative – Immunocytochemically: CD68+++ Results. The definitive morphological typing of the macrophages as high molecular PVP-containing macrophages could only approved by the investigation of the ultrastructure in transmission electron microscopy (direct indicator for PVP; i.e. evidence): intracytoplasmic globules of different size and periodic lamellate internal structure. Conclusions. The results of this study are essential for the manufacture of dialyse membranes by advancement the adhesion of PVP and for the patients to prohibit the generalized PVP-thesaurismosis. Also the findings are helpful for the clinicians, notably for nephrologists in the surveillance of chronic hemodialysed patients, for gastroenterologists and for pathologists to receive an algorithm of the diagnostic relevant panel. FR-P-045 Interaction of cathepsin X with galectin-2 in H. pylori dependent gastric carcinogenesis A . Teller1 , D . Kuester1 , A . Roessner1 , S . Krueger1 1Otto-v .-Guericke University, Department of Pathology, Magdeburg Aims. Our previous studies have shown an association between Helicobacter pylori infection, the strong up-regulation of cathepsin X (CTSX), and the development of gastric cancer. The physiological function of CTSX still needs to be clarified. In a yeast two-hybrid screen we could identify galectin-2 as a novel interaction partner of cathepsin X. Now we suppose an interactive role of CTSX and galectin-2 in modulation of the immune system in response to H. pylori-infected gastric epithelial cells. Methods. Background for further experiments was the screening of the yeast two-hybrid system, where we could identify galectin-2 as a novel interaction partner of CTSX. Using Western blots and immunohistochemistry we want to analyze galectin-2 levels in biopsy specimens of H. pylori-infected and non-infected patients as well as in gastric cancer Der Pathologe · Supplement 1 · 2012 | 97
Abstracts samples which showed increased CTSX levels in disease progression. Functional consequences of the interaction of CTSX and galectin-2 were tested on siRNA treated primary human epithelial and immune cells in confrontation and migration experiments with and without infection with H. pylori. Results. Interaction of CTSX and galectin-2 was clearly characterized by immunoprecipitation, double immunofluorescence and pull-down assays. Immunohistochemistry and western blots on tissue samples indicated an inversely expression of CTSX and galectin-2. H. pylori-negative samples showed low expression of CTSX but high expression of galectin-2, whereas galectin-2 expression decreased and CTSX increased with progression of disease. Macrophages with high expression of CTSX rapidly migrate into epithelial cell monolayers and down regulate whereby their galectin-2 levels. Conclusions. The interaction of CTSX and galectin-2 seems to be a major regulatory element to regulate the activity of the immune system against H. pylori colonization and cancer development. As both enzymes known to be effecting T-cell function and spreading our further experiments will focus on possible mechanisms to induce an efficient anti-tumoral immune response by influencing CTSX/galectin-2 signalling. FR-P-046 The impact of HER2 amplification in the dysplasia-carcinomasequence in the stomach T . Vlajnic1 , S . Eppenberger1 , S . Schneider1 , L . Terracciano 1 , L . Tornillo1 , G . Cathomas2 1 2 Institute of Pathology, University Hospital Basel, Switzerland, Cantonal Institute of Pathology, Liestal, Switzerland Aims. HER2 amplification and overexpression was demonstrated in gastric carcinoma soon after its discovery in breast carcinoma. There is growing evidence that HER2 has an important role in tumorigenesis in gastric cancer with a reported prevalence of amplification/overexpression in 7–34%. However, the role of HER2 in the progression of dysplasia to gastric carcinoma has not yet been investigated. The aim of this study was to determine the HER2 status in precursor lesions of gastric carcinoma, i.e. in gastric dysplasia and early cancer. Methods. A tissue microarray consisting of gastric carcinomas (n=370) was evaluated immunohistochemically and by FISH and SISH analysis for the HER2 status. Whole tissue sections with gastric cancer (n=206) were then re-evaluated for gastric dysplasia and in case of presence of dysplasia next to carcinoma an immunohistochemical analysis was performed. Additionally, immunohistochemistry and SISH analysis was performed on gastric biopsies with dysplasia (n=62) without coexisting carcinoma. Results. HER2 amplification was found in 7.9% of gastric carcinomas. 50 cases showed gastric dysplasia next to carcinoma and the HER2 status in the dysplasia was the same as in the respective invasive carcinoma. However, the prevalence of HER2 amplification in the cases of dysplasia alone was only 3.2%. Conclusions. Interestingly, our data indicate that HER2 amplification/ overexpression may be an early event and may induce a rapid progression from dysplasia to invasive carcinoma in the stomach. Further studies are needed to elucidate the potential role for the anti-HER2 targeted therapy in patients with gastric dysplasia. 98 | Der Pathologe · Supplement 1 · 2012 FR-P-047 Epstein-Barr virus (EBV) in the development of gastric cancer M . Cathomas1 , V . Genitsch1 , L .M . Terracciano 2 , L . Tornillo2 , A . Lugli2 , A .H . Marx3 , G . Sauter3 , F . Carneiro4 , F . Hofstädter5 , N . Willi1 , G . Cathomas1 1 2 Institute of Pathology, Liestal, Switzerland, Institute of Pathology, University Basel, Switzerland, 3Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, 4Institute of Molecular Pathology of the University of Porto (IPATIMUP), Portugal, Portugal, 5Institute of Pathology, University Regensburg, Regensburg Aims. Epstein-Barr virus (EBV) infections are associated with a number of tumours, including lymphoproliferative diseases and nasopharyngeal carcinomas. In addition, a subset of gastric tumours has been associated with EBV, ranging from 1.3% to 20.2% of all gastric cancers. The role of EBV in the development and progression of gastric cancer, however, remains to be elucidated. Aim of the study was the assessment of the prevalence of EBV associated gastric cancers and the presence of the virus in the development of individual tumours. Methods. Based on tissue micro arrays (TMA), the presence of EBV was evaluated in gastric cancers of 5 institutions within Europe (Liestal and Basel, Switzerland; Hamburg and Regensburg; Porto, Portugal) by using a commercial in situ hybridization assay for EBER. In a second step, nontumorous and tumorous tissue including dysplasia, intramucosal and invasive carcinomas as well as metastasis were analyzed for the presence of EBV. Results. A total of 610 (91.6%) of 666 tumours on TMAs were available for analysis. Overall, 4.9% of gastric cancers were positive for EBER, ranging form 2.2% to 9.1% within the different institutions. No age difference was observed within EBV positive and negative patients [68.2 vs. 66.2 (n=23/515)], but EBV positive tumours showed a male predominance [87.0% vs. 60.6%; p
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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
Page 48 and 49: DO-002b Impact of terminologies in
Page 50 and 51: Methods. We performed MCPyV-FISH of
Page 52 and 53: FR-013 HPV-genotype distribution in
Page 54 and 55: Methods. Three different techniques
Page 56 and 57: (i.e. investment in equipment and e
Page 58 and 59: FR-032 COLD-PCR: a powerful tool in
Page 60 and 61: dissection (MBLND) technique to imp
Page 62 and 63: SO-005 Prevalence of mutations in s
Page 64 and 65: SO-011 Methylation profiling and in
Page 66 and 67: more effective than SAHA alone and
Page 68 and 69: SO-022 Specialized pathology review
Page 70 and 71: SO-027 Ki-67 in mitotic score group
Page 72 and 73: nificantly associated with advanced
Page 74 and 75: liver did not correlate with the mu
Page 76 and 77: AG Paidopathologie II SO-046 Overex
Page 78 and 79: Results. Histomorphology of the ova
Page 80 and 81: p42 and p27 have not yet been inves
Page 82 and 83: SO-068 Recent advances in understan
Page 84 and 85: SO-075 A novel, dual role of CCN3 i
Page 86 and 87: Pancreatic Adenocarcinoma SG-137 Se
Page 88 and 89: sease and 30 colon cancer serum sam
Page 90 and 91: Conclusions. Although CRC is charac
Page 92 and 93: differentiated and TNM stage III or
Page 94 and 95: pressed moderate levels of the prot
Page 96 and 97: FR-P-037 MALDI imaging reveals COX7
Page 100 and 101: on primary cells of wild-type and c
Page 102 and 103: chemotherapy was recommended and co
Page 104 and 105: aims are twofold: 1) to verify the
Page 106 and 107: Results. Her2/neu status in TMAs an
Page 108 and 109: prognostic impact was found in rect
Page 110 and 111: provided information on survival ti
Page 112 and 113: Methods. Biopsy specimens from 430
Page 114 and 115: the OS rate was 53% for patients wi
Page 116 and 117: FR-P-098 Immunohistological stainin
Page 118 and 119: FR-P-104 Histopathological evaluati
Page 120 and 121: within the earliest morphologic det
Page 122 and 123: Conclusions. In primary imaging a g
Page 124 and 125: fibrotic neointma development as we
Page 126 and 127: FR-P-129 Alpha-1-antitrypsin-PiZ-an
Page 128 and 129: FR-P-136 The expression of central
Page 130 and 131: cosa and in the periarterial tissue
Page 132 and 133: FR-P-149 Combination of Castleman d
Page 134 and 135: or without different concentrations
Page 136 and 137: Results. In 18 cases (79%) the caus
Page 138 and 139: FR-P-168 Autopsy findings in a 2-ye
Page 140 and 141: FR-P-174 MPGN-like glomerulonephrit
Page 142 and 143: Poster: Gynäkopathologie und Mamma
Page 144 and 145: SA-P-011 Genetic aberrations of pre
Page 146 and 147: Mechanismen, die eine Progression d
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internet server. A network of inter
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Methods. HE-gefärbte Schnittpräpa
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Conclusions. The newly released 450
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and desmoplastic reaction are diffe
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one patient revealed more than 9 mi
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situation, the V600E mutation in th
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SA-P-064 Evolution of molecular pat
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nic markers such as myf4 and MyoD1
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Conclusions. To our knowledge, this
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SA-P-085 Expression of the eukaryot
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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
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96. Jahrestagung der Deutschen Gesellschaft für Pathologie e. V ...

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