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

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DO-108 Identification of potential criteria for a successful Rituximab salvage therapy in kidney allograft rejection M . Dämmrich 1 , C . Blume 2 , C . Bockmeyer 1 , S . Immenschuh 3 , A . Schwarz 2 , D . Agustian 1 , V . Broecker 1 , H . Kreipe 1 , J . Becker 1 1 Hannover Medical School, Institute for Pathology, Hannover, 2 Hannover Medical School, Centre for Internal Medicine, Hannover, 3 Hannover Medical School, Institute for Transfusion Medicine, Hannover Aims. Rituximab (anti-CD-20 antibody) is often used in kidney transplantation to treat rejection refractory to standard treatment. Rituximab therapy carries a risk for serious infectious complications and is not effective in all cases. Therefore clinica, serological or histopathological criteria to predict Rituximab response are most desirable. As a first step for the identification of useful criteria we did a retrospective exploratory analysis to identify criteria that were different between Rituximab responders and non-responders. Methods. 18 renal transplant recipients who received Rituximab (375 g/ m2 body surface, 1–2 courses after steroid bolus therapy, 15× combined with up to 5 courses of plasmapheresis) for standard-therapy resistant rejection were included in the study with their last biopsy before therapy. 10 were identified by terminal loss of transplant function as nonresponders, 8 as responders. Clinical, serological and histopathological parameters were compared between both cohorts by Wilcoxon- or χ2 tests. P-values were regarded as descriptive in this retrospective analysis. Results. At time of biopsy more of the Rituximab non-responders had panel-reactive antibodies (>85%), and their serum creatinine before therapy was higher. Among the histopathological criteria tubulitis was less severe in responders. No significant differences were found for any of the other clinical, serological or histopathological criteria. Conclusions. In this retrospective exploratory study we identified lower serum creatinine before therapy, the presence of panel- reactive antibodies in more than 85% at time of biopsy, and a less severe Banff t-score as possible criteria to predict responsiveness to Rituximab therapy. These criteria need validation in future prospective randomized studies. DO-109 Splenectomy and postconditioning with the sphingosine-1-phosphate agonist FTY720 protect the myocardium against ischemia reperfusion injury D . Goltz1 , S . Huss2 , E . Ramadori1 , L . Diehl3 , R . Büttner2 , R . Meyer4 1 2 University of Bonn, Dept . of Pathology, Bonn, University of Cologne, Dept . of Pathology, Köln, 3University of Bonn, Institute of Molecular Medicine, Bonn, 4University of Bonn, Physiology II, Bonn Aims. The pathogenesis of myocardial ischemia reperfusion injury (MI/R) involves the inflammatory response of the innate immune system. A modulation of this response could be a potential future target in the management of the acute coronary syndrome. Recently, the spleen has been proved an important origin of a Ly6-Cpos monocyte subset that readily invades the injured myocardium upon ischemic damage. We operated a murine myocardial ischemia reperfusion model in splenectomised animals to reduce the invasion of phagocytic active immune cells. In a second pharmacologic approach we applied the sphinosine-1phosphate analogue FTY720 with reperfusion to interfere with the maturation of monocytic derived macrophages. The aim of this study was to evaluate the short and long term outcome of MI/R after modulation the immune response. Methods. In a murine closed-chest ischemia-reperfusion model, myocardial infarct volume was assessed by TTC staining after 24 h of reperfusion and by planimetric quantification of fibrosis on the Masson stained specimen after 21 days of reperfusion in control animals, splenectomised animals and FTY720 treated mice. Within the same interval, cardiac function was evaluated by catheterisation using a Millar cathe- ter. The immune response was characterised by FACS analysis in whole heart specimens after 24 h. Results. After 24 h of reperfusion, splenectomised animals and FTY720 treated animals revealed a significant reduction of infarct volume. The invasion of monocytes, especially of Ly6-Cpos monocytes was significantly reduced in splenectomised animals compared to the control group. Moreover, the ratio of inflammatory macrophages to resident macrophages was significantly smaller in the splenectomised group. FTY720 treated animals showed an almost exclusive invasion by monocytes within the remote myocardium. Functional data show a significantly improved systolic cardiac function in both, the splenectomised and the FTY720 treated groups compared to the control animal after 21 days of reperfusion. Quantification of the area of fibrosis, however, revealed a trend towards reduced myocardial scarring in both target groups, but the decline failed to reach a level of significance. Conclusions. Both, splenectomy and postconditioning with FTY720 are cardioprotective within 3 weeks after MI/R. In splenectomised animals, this effect is due to a reduction of early invading monocytes. The mechanism of FTY720 efficiency still warrants further investigation. DO-110 Nestin expression in fetal and adult lungs vessels as well as vascular tumors S . Gerlach1 , G . Kristiansen1 , A .M . Müller2 1University Bonn Medical Center, Institute of Pathology, Bonn, 2University Bonn, Department of Pediatric Pathology, Bonn Aims. The neural stem/progenitor cell marker Nestin is a class VI intermediate filament protein. It is not only expressed by undifferentiated central nervous system (CNS) cells during development and adult CNS cells but various tumour cells as well as in injured and regenerating tissues, indicating nestin as a marker for activated, migrating, proliferating cells. Recently it has been described in proliferating endothelial cells (EC). We were interested in any differences Nestin expression in fetal and adult vessels as well as vascular tumors. Methods. Endothelial Nestin and D2-40 expression was studied by immunolocalisation in chorionic tissue from early abortions (n=5), fetal (n=21) and adult (n=3) lungs, infantile hemangiomas (n=5) and angiosarcomas (n=5). Results. Although Nestin was expressed by EC of all blood vessels but not lymphatic vessels there were differences concerning expression intensity. In the first trimester, EC in chorionic and villous tissue as well as EC of pulmonary veins, arteries and capillaries showed the same strong Nestin-positivity. Starting in the second half of the second trimester Nestin expression in venous EC began to fade, while arterial EC still showed a strong staining. In lungs of neonates and adults the Nestin expression was even weaker, although in arteries it was still stronger expressed than in veins. In angiosarcomas Nestin was strongly expressed by the tumour cells. EC of all infantile hemangiomas were clearly but in comparison to angiosarcomas weaker stained. Conclusions. The intermediate filament Nestin can be regarded as endothelial marker expressed by vascular EC already during the first weeks of life. As it is not expressed by lymphatic EC it can help discriminating blood vessel endothelium from lymphatic endothelium. In accordance with other endothelial markers like Angiotensin I converting enzyme it is weaker expressed in adult pulmonary veins than adult pulmonary arteries. The strong Nestin expression in fetal vessels – when compared to EC of mature vessels or hemangiomas – corresponds to a strong Nestinpositivity in malignant endothelial tumor cells. At present we analyse the role of Nestin in colorectal cancer resp. its tumour vessels concerning expression patterns in different stages of cancer. Der Pathologe · Supplement 1 · 2012 | 41
Abstracts AG Molekularpathologie DO-111 Improved method of detecting the ERG gene rearrangement in prostate cancer using combined dual-color chromogenic and silver in-situ hybridization M . Braun 1 , J . Stomper 1 , D . Böhm 1 , W . Vogel 1 , V . Scheble 2 , N . Wernert 1 , Z . Shaikhibrahim 1 , F . Fend 3 , G . Kristiansen 1 , S . Perner 1 1 University Hospital Bonn, Institute of Pathology, Bonn, 2 University Hospital Tübingen, Division of Hematology and Oncology, Tübingen, 3 University Hospital Tübingen, Institute of Pathology, Tübingen Aims. The recently detected TMPRSS2-ERG fusion revealed as a recurrent and prevalent prostate cancer (PCa) specific event, which potentially qualifies it for clinical utilizations. To detect this alteration, fluorescence in-situ hybridization (FISH) is the method of choice. However, FISH harbors some disadvantages for widespread adoption in clinical practice. Subsequently, the chromogenic in-situ hybridization (CISH), that uses organic chromogens, and the enzymatic metallography silver in-situ hybridization (SISH) emerged as promising bright-field alternatives. Compared to CISH, SISH signals are very distinct and superior with regard to signal clarity and resolution, but rule out a multi-color protocol. However, the precise localization of genomic targets using a dual-color approach is indispensable for gene break-apart and fusion assays. In order to bridge this gap, we aimed to develop a dual-colour combined CISH and SISH (CS-ISH) gene break-apart assay on the example of the ERG gene commonly rearranged in PCa. Methods. On the basis of the ERG break-apart FISH assay, we established a dual-colour ERG break-apart CS-ISH assay and compared these results with those obtained by FISH. We assessed 178 PCa and 10 benign specimens for their ERG rearrangement status applying a dual-colour FISH and CS-ISH ERG break-apart assay on consecutive sections. Results. We observed a highly significant concordance (97.7%) between FISH-based and CS-ISH-based results (Pearson’s correlation coefficient 0.955, p
Page 2 and 3: Inhalt Der Pathologe · Supplement
Page 4 and 5: Inhalt Der Pathologe · Supplement
Page 6 and 7: Editorial Liebe Kolleginnen und Kol
Page 8 and 9: Kolorektales Karzinom 2 VO-005 Tran
Page 10 and 11: Keynote Lecture VO-014 Genetic dete
Page 12 and 13: (AMACR, FASN, GOLM1, GSP-pi, ERG) t
Page 14 and 15: to assess the correct rate of R1 re
Page 16 and 17: DNA damage, and cytotoxic drugs. Au
Page 18 and 19: HCV-positive formalin-fixed and par
Page 20 and 21: well as MET activation were examine
Page 22 and 23: or BRAF mutation, c-MYC and SIRT1 e
Page 24 and 25: AG Pneumopathologie III DO-032 Remo
Page 26 and 27: immature granulopoiesis showed a st
Page 28 and 29: ned, if well-defined mantle zones,
Page 30 and 31: phomas). Most prominent gains or am
Page 32 and 33: DO-062 Tumor-associated macrophages
Page 34 and 35: DO-080 DOG1: an immunohistochemical
Page 36 and 37: AG Oralpathologie DO-087 Detection
Page 38 and 39: DO-094 Do activated fibroblasts inf
Page 40 and 41: DO-101 Histopathological analysis o
Page 44 and 45: Conclusions. In conclusion, 454 par
Page 46 and 47: 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 98 and 99:
in the context of therapy response
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
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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
Page 148 and 149:
internet server. A network of inter
Page 150 and 151:
Methods. HE-gefärbte Schnittpräpa
Page 152 and 153:
Conclusions. The newly released 450
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and desmoplastic reaction are diffe
Page 156 and 157:
one patient revealed more than 9 mi
Page 158 and 159:
situation, the V600E mutation in th
Page 160 and 161:
SA-P-064 Evolution of molecular pat
Page 162 and 163:
nic markers such as myf4 and MyoD1
Page 164 and 165:
Conclusions. To our knowledge, this
Page 166 and 167:
SA-P-085 Expression of the eukaryot
Page 168 and 169:
Results. The papillary RCC type II
Page 170 and 171:
SA-P-098 Male infertility: assessme
Page 172 and 173:
SA-P-104 Process oriented scientifi
Page 174 and 175:
Conclusions. The IBDW offers a uniq
Page 176 and 177:
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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