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

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SA-P-064 Evolution of molecular pathology at the Institute of Basel M .P . Bihl 1 , S . Hoeller 1 , A . Foerster 1 , R . Chaffard 1 , S . Schneider 1 , A . Rufle 1 , L . Terracciano 1 , L . Tornillo 1 1 University of Basel, Institute of Pathology, Basel, Switzerland Aims. Molecular genetics in pathology is a very young field. It began with analysis of haematological diseases or inherited disorders, but in the last decade, also many of solid tumors have been found to be related to specific somatic mutations. These mutations can give a hint to drug sensitivity in a given tumor and therefore are urgently required in modern oncology. Here we show how this field has developed in the recent years using the example of the activity of the Institute of Pathology during the last 6 years. Methods. The number of PCR based analysis increased from 206 (in 2006) to over 800 analyses (in 2011). Results. In the beginning only CKIT/PDGFRA mutation and EGFR mutation analysis and clonality analysis were performed. However, the overall percentage of analysed sites remained stable with 50% from the lung, 10–20% from the blood or lymph node and 10–25% from colorectal or gastrointestinal sites. Recently, new mutations are also routinely tested like (IDH 1 and 2, BRAF and CTNNB1) and therefore new organs were included like brain (glioma), skin (melanoma) and liver (adenomas). From three available assays in 2006 the spectrum of our analysis expanded to 20 different assays today. The number of performed FISH analysis stayed stable, while the number of HER2 hybridisations dropped, but new assays were introduced into the routine panel like 1p19q and ALK translocation analysis for glioma and adenocarcinoma of the lung, respectively. Therefore, the dynamic changes in molecular pathology are due to new tumor classification systems, the development of new tumor specific drugs and the increased knowledge of drug sensitivity in cancer patients harboring specific somatic mutations. Conclusions. In the upcoming years molecular based prognostic markers and mutation specific therapies will even more expand the spectrum of molecular testing in pathology. Its role is crucial to improve and optimize the diagnosis and therapy of tumors and is essential in modern oncology. Adaptation of the increasing knowledge of pathogenetic pathways will be a major issue for molecular laboratories in the future. SA-P-065 The amyloid precursor protein (APP) is a novel biomarker for transformed human pluripotent stem cells V . Venkataramani1 , K . Thiele2 , C .-L . Behnes2 , G .G . Wulf1 , P . Thelen3 , L . Opitz4 , G . Salinas-Riester4 , O . Wirths5 , T .A . Bayer5 , H .-J . Radzun2 , S . Schweyer2 1University Medicine Göttingen, Department of Hematology and Oncology, Göttingen, 2University Medicine Göttingen, Department of Pathology, Göttingen, 3University Medicine Göttingen, Department of Urology, Göttingen, 4 5 University Medicine Göttingen, DNA Microarray Facility, Göttingen, University Medicine Göttingen, Division of Molecular Psychiatry, Göttingen Aims. There is no doubt that the amyloid precursor protein (APP) and its proteolytically derived Aβ species significantly contribute to the pathogenesis of Alzheimer disease. However, the normal physiological role of this ubiquitously expressed protein has remained largely unknown. In the current study, we characterized APP expression in a panel of human testicular germ cell tumors (TGCT) of different histological origin. Furthermore, we analysed whether histone deacetylase (HDAC) inhibitors effectively induce cell differentiation and impact stem cell signature and APP protein levels in embryonal carcinoma (EC) cell lines. These analyses were also performed in a physiologically relevant in vivo setting using an established xenograft mouse model. Methods. Paraffin-embedded tissue blocks from orchiectomy specimens were used for tissue microarray construction consisting of 173 cases of pure and mixed TGCTs as well as eight randomly selected normal testicular tissues. Following TGCT cell lines were used: NCCIT, NTera-2 (EC cell lines) and TCam-2 (seminoma cell line). Cellular differentiation was analysed by cell proliferation and cytotoxicity assays, cell morphology via fluorescence microscopy and expression analyses of stem cell genes and lineage-specific differentiation markers were determined using microarray analysis, qRT-PCR and Western blot analysis. APP expression was selectively down-regulated using target-specific siRNA duplexes. Xenografts inoculated with NTera-2 were orally treated with the HDAC inhibitor VPA and tumor growth as well as APP protein levels were compared to vehicle treated animals. Results. APP is exclusively expressed in pluripotent germ cell cancer subtypes (EC and seminoma). Differentiated TGCTs (e.g. teratoma) only presented low or lack of APP expression. APP knock-down induced the expression of lineage-specific differentiation markers. HDAC inhibitor treatment induced cell differentiation, accompanied by down-regulated APP protein levels and stem cell genes. Moreover, GRP78 could be identified as a key factor that specifically triggers proteasomal degradation of APP. Oral administration of VPA significantly suppressed tumor growth and depleted APP protein levels in vivo. Conclusions. Our results indicate that APP behaves as a reliable biomarker for transformed human pluripotent stem cells and also shed light on the significance of APP as a novel molecular target and furthermore broaden the therapeutic potential of HDAC inhibitors in the clinical treatment of TGCT. SA-P-066 Thymoquinone lowers toxicity and increases efficacy of 5-fluorouracil C . El-Baba1 , S . Morgenthal2 , M . Ocker3 , H . Gali-Muhtasib4 , R . Schneider-Stock 1 1 2 University of Erlangen-Nuremberg, Institute of Pathology, Erlangen, Christian-Albrechts-University, Institute of Pathology, Köln, 3Phillips-University of Marburg, Institute of Surgical Research, Marburg, 4American University of Beirut, Department of Biology, Beirut, Lebanon Aims. Colorectal cancer is a non-negligible cause of mortality worldwide. 5-fluorouracyl (5-FU) has proved to be one of the most effective chemotherapeutics for colorectal cancer but an inactivated p53 status leads to a resistance to 5-FU. We have shown that thymoquinone (TQ), a bioactive compound extracted from Nigella sativa (black seed) exerts promising anti-apoptotic effects independent of the p53 status of tumor cells. Our aim is to investigate if TQ is able to sensitize colorectal cancer cells to 5-FU to minimize its cytotoxic side-effects in the clinical setting. Methods. Human colon cancer cells HT29 (mutant p53), HCT116 (p53+/+) and normal intestinal cells HCEC were treated with TQ and/or 5-FU. Cell viability was measured via crystal violet, mitochondrial activity and colony formation assays. Cell cycle distribution and apoptosis were assessed by flow cytometry via propidium iodide (PI), Annexin-V staining, and Western blotting. A mouse xenograft study was conducted for a better assessment of potential in vivo effects. Results. HCT116wt cells were more sensitive to TQ than HT29 cells. HCEC cells were highly resistant to TQ treatment, which indicates that TQ has an effect mainly on cancerous cells. In HT29 cells, the combination TQ/5-FU was equally efficient as the treatment with ten times higher concentration of 5-FU alone. Annexin-V, propidium iodide-cell cycle analysis, as well as Caspase 3 and Caspase 9 cleavage along with the increase of Bax to Bcl2 ratio, revealed a higher apoptosis induction when the cells are treated with both drugs in comparison to either TQ or 5-FU. In vivo study showed that the relative tumor size of mice co-treated with TQ and 5-FU was significantly reduced in comparison with the tumors of control mice or mice treated with either drug alone. Conclusions. TQ when combined with the antineoplastic agent 5-FU was increasing apoptosis in colon cancer cells. The combination therapy could overcome the resistance to 5-FU in the p53 mutant tumor cells without showing dramatic cytotoxicity on normal colon cells. Combined with further clinical studies this approach might be promising for the improvement of colorectal cancer treatment. Der Pathologe · Supplement 1 · 2012 | 159
Abstracts SA-P-067 Overexpression of anti-apoptotic CIAP2 is typical of thymic squamous cell carcinoma but not thymomas – hints to functional relevance D . Belharazem 1 , B . Huang 2 , L . LI 3 , P . Stroebel 1 , A . Marx 1 1 University Medical Center Mannheim; University of Heidelberg, 2 Institut of Pathology; University of Würzburg, 3 Medical Research Center, Medical Faculty Mannheim Aims. Thymomas and thymic carcinomas (TCs) are epithelial tumors of the thymus. Their molecular oncogenesis is poorly understood. Recent extensive sequencing of a broad spectrum of receptor and non-receptor kinase genes in thymomas and TCs (Girard N et al, Clin Cancer Res 15:6790, 2009) failed to identify recurrent mutations except for known activating KIT mutations in
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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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SO-022 Specialized pathology review
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SO-027 Ki-67 in mitotic score group
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nificantly associated with advanced
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liver did not correlate with the mu
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AG Paidopathologie II SO-046 Overex
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Results. Histomorphology of the ova
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p42 and p27 have not yet been inves
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SO-068 Recent advances in understan
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SO-075 A novel, dual role of CCN3 i
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Pancreatic Adenocarcinoma SG-137 Se
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sease and 30 colon cancer serum sam
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Conclusions. Although CRC is charac
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differentiated and TNM stage III or
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pressed moderate levels of the prot
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FR-P-037 MALDI imaging reveals COX7
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in the context of therapy response
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on primary cells of wild-type and c
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chemotherapy was recommended and co
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aims are twofold: 1) to verify the
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Results. Her2/neu status in TMAs an
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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
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
Page 154 and 155: 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 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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