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

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sease and 30 colon cancer serum samples were included for additional specificity testing. Results. Based on the training study we could evaluate the top candidate biomarkers with the best values for sensitivity and specificity. A marker panel of DKK3 and ITIH5 detected breast cancer with a sensitivity of 46% (55/120). Specificity of the panel was sufficient with 83%, 100% and 93% in colon cancer samples, benign and healthy control samples, respectively. Control samples revealed unacceptable high methylation rates of SFRP1 and SFRP5 in DNA extracted from colon cancer sera, whereas SFRP2 and WIF1 showed a considerable methylation frequency in sera from healthy controls. Conclusions. The current study suggests that cancer-specific methylation of ITIH5 and DKK3 in serum-derived tumor-borne DNA might be valuable biomarkers for the early detection of breast cancer. In the second phase of this project we are currently validating ITIH5 and DKK3 as reliable methylation biodiagnostic markers in an independent test set consisting of 160 breast cancer serum samples and 160 control samples. SG-145 Slug and SOX9 in aggressive breast carcinoma V . Tischler1 , A . Noske1 , U . Zürrer-Härdi1 , F . Ingold1 , J .-P . Theurillat1 , H . Moch1 , Z . Varga1 , W . Guo2 1University Hospital Zurich, Institute of Surgical Pathology, Zürich, Switzerland, 2Albert Einstein College of Medicine, Ruth L . and David S . Gottesman Institute for Stem Cell Biology and Regenerative Medicine, New York, United States Aims. Co-expression of the transcription factors Slug and Sox9 was recently used to determine mammary stem cell state. Our intention was to study the expression of Slug and Sox9 in primary breast cancer and to correlate it with clinicopathological parameters including overall survival. Methods. Formalin-fixed paraffin embedded tumor tissue of 306 patients with primary breast cancer [pT1 132 (43.1%), pT2 134 (43.8%), pT3 21 (6.9%), pT4 19 (6.2%); pN0 92 (34.1%), pN1 136 (50.4%), pN2 22 (8.1%), pN3 20 (7.4%); G1 41 (13.4%), G2 144 (47.1%), G3 121 (39.5%)] were assembled on a tissue microarray (TMA). Mean follow-up was 40 months (range 4–324 months). Immunohistochemical Slug and Sox9 expression was semi-quantitatively evaluated. The median value was used as cut-off point for dichotomization into “low Slug”/”high Slug” and “low Sox9”/”high Sox9” expressing groups. Results. Slug and Sox9 expression was identified in the tumor cell nuclei. High Slug expression was found in 41% of the cases (126/306) and high Sox9 expression in 74% (226/306). High expression of both Slug and Sox9 was found in 92/306 (30.1%). Co-expression of Slug and Sox9 significantly correlated with higher tumor grade (p
Abstracts our study to identify overlapping molecular characteristics in a variety of histologically defined lymphoma entities. To achieve this goal, comprehensive expression profiles of non-coding and coding transcripts derived from a broad spectrum of lymphomas were established. Our data show that overlapping molecular features can be identified beyond the current lymphoma classification. Methods. RNA was extracted from frozen tissue blocks of distinct human B- and T-cell lymphoma entities as well as tonsils (n=116). The small (micro) RNA fraction was sequenced by next generation technology (SOLiD) and total RNA was subjected to Affymetrix Exon 1.0 ST array hybridisation. In addition immunohistochemical and clinical data was acquired. Bioinformatic analyses were then applied for subgroup detection. Results. Unsupervised clustering based on the mature micro RNA expression derived from deep sequencing demonstrated the presence of two distinct large clusters within the case collection. One cluster contained predominantly the so-called indolent lymphoma types, but also a considerable number of aggressive B-cell lymphoma cases. In the second cluster the majority of cases were aggressive B-cell lymphoma but interestingly intermingled with the T-cell lymphoma cases. Differentially expressed micro RNAs between the two clusters were determined and logistic regression identified a micro RNA classificator able to distinguish the two groups. The micro RNA expression data was combined with the coding RNA data in order to identify the involved pathways. Conclusions. Micro RNA expression profiles obtained by deep sequencing were able to identify two groups within a lymphoma collection that separated the cases beyond the histopathological classification system. Discriminative micro RNAs and associated pathways were identified. These findings give new insights into lymphoma biology and point to alternative treatment options. *These authors contributed equally to the study . Poster Poster: Deutsch-Chinesisches Symposium SG-P-112 Mitochondrial mortalin (HSPA9) expression in enterocytes is regulated by ACSL5 N . Gaßler 1 , C . Klaus 1 , E . Kämmerer 2 , M . Adolf 1 , A . Reinartz 1 1 RWTH Aachen University, Institute of Pathology, Aachen, 2 RWTH Aachen University, Klinik für Kinder- und Jugendmedizin, Aachen Aims. Mitochondrial acyl-CoA synthetase 5 (ACSL5), a long-chain fatty acid activating enzyme, is preferentially found in small intestinal enterocytes. ACSL5 activities are associated with complex changes in the mitochondrial lipid metabolism and are important for epithelial differentiation and cell death. The aim of the present study was to identify and characterize ACSL5 related regulation of mitochondrial proteins. Methods. Mitochondria isolated from ACSL5 transfected CaCo2 cells and controls were homogenized and further separated with 2D-gel electrophoresis. Spots were analyzed using special proteomics software. Protein spots differentially expressed were further identified with MAL- DI-TOF. Additional techniques were used for target validation. Laser microdissected enterocytes from normal human small intestinal mucosa were investigated to substantiate the in vitro findings. Results. 14 mitochondrial protein species, probably regulated by ACSL5, were identified. ACSL5 dependent expression and synthesis of the candidate molecule mortalin (HSPA9) was confirmed using qRT-PCR, Western blotting, and siRNA ACSL5 knockdown. Using this approach, a positive correlation of ACSL5 and mortalin expression was verified. The positive correlation of ACSL5 and mortalin expression was additio- 88 | Der Pathologe · Supplement 1 · 2012 nally found in human normal small intestinal mucosa. Strong mortalin expression was seen in ACSL5-rich enterocytes isolated from intestinal villi, whereas mortalin was diminished in low ACSL5 expressing enterocytes isolated from intestinal crypts. Conclusions. In conclusion, ACSL5 activities are associated with changes in lipid metabolism as well as expression of mitochondrial proteins. ACSL5-dependent expression and synthesis of mitochondrial mortalin is probably a phenomenon of stress-response. SG-P-113 ACSL5 as putative modifier of Wnt activity in intestinal cells C . Klaus1 , U . Schneider1 , R . Knuechel1 , N . Gaßler1 1RWTH Aachen University, Institute of Pathology, Aachen Aims. The mitochondrial localized Acyl-CoA synthetase 5 (ACSL5) converts free long-chain fatty acids into fatty acyl-CoA esters, and thereby plays a key role in lipid biosynthesis and fatty acid degradation. In particular, ACSL5 has been recently identified to be involved in apoptotic cell death of senescent enterocytes along the intestinal crypt-villus axis and to interact with mitochondrial proteins. The aim of this study was to investigate ACSL5-dependent effects on intestinal signalling pathways that coordinate proliferation and/or differentiation of enterocytes, particularly the Wnt pathway. Methods. Wnt signalling was analysed in an ACSL5 overexpressing cell culture model using luciferase assays, immunohistochemistry, qRT-PCR and Western blot. The findings were substantiated with expression studies in human colon carcinomas and in a Wnt-associated mouse model. Results. ACSL5 transgenic intestinal-derived cells displayed a strong susceptibility to pro-apoptotic stimuli. This phenomenon was accompanied by caspase-3 activation and significant down-regulation of Wnt signalling activity. In particular, Wnt pathway associated mitochondrial localized molecules were identified as interaction partners of ACSL5 activity. Conclusions. Molecular mechanisms underlying ACSL5-dependent apoptosis susceptibility of enterocytes are probably bivalent including pro-apoptotic and anti-proliferative activities. SG-P-114 MAPK signaling regulates differential WNT activity in colorectal cancer D . Horst1 , J . Chen2 , T . Kirchner1 , R . Shivdasani2 1Ludwig-Maximilians-Universität München, Pathologisches Instiut, München, 2Harvard Medical School, Dana-Farber Cancer Institute, Boston, United States Aims. Most colorectal cancers (CRCs) express the WNT effector protein β-catenin in a heterogeneous pattern. Strong nuclear expression is often confined to a small fraction of tumor cells at the tumor’s leading edge. Recent data suggest a role for Mitogen Activated Protein Kinase (MAPK) signaling in nuclear accumulation of β-catenin. We therefore investigated if MAPK activity regulates overtly differential WNT activity in CRC cell subpopulations. Methods. We used gene expression profiling, and immunohistochemistry to assess interdependence of MAPK and WNT pathway activity in CRC. Lentivirus- and drug-based pathway modification in CRC xenograft tumors of primary human colon cancers and colon cancer cell lines was used to study the effect of MAPK activation or repression on differential WNT activity. Results. CRC cells with high WNT activity showed coincident overexpression of MAPK target genes and high levels of phospho-ERK, indicating active MAPK signaling. Forced MAPK activation by lentiviral expression of constitutively active KRAS enhanced WNT pathway activity in vivo in CRC xenograft tumors, whereas drug based inhibition of EGFR signaling attenuated it.
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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
Page 38 and 39: DO-094 Do activated fibroblasts inf
Page 40 and 41: DO-101 Histopathological analysis o
Page 42 and 43: DO-108 Identification of potential
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 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
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
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FR-P-168 Autopsy findings in a 2-ye
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FR-P-174 MPGN-like glomerulonephrit
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Poster: Gynäkopathologie und Mamma
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SA-P-011 Genetic aberrations of pre
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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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