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

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Methods. Three different techniques FISH, CISH and SISH for in situ hybridization were evaluated regarding their use in routine pathology. Furthermore, a multi-colour probe in malignant melanoma samples was evaluated as test tool in histological borderline melanoma cases and a computer based algorithm was implemented for simplifying and standardization. Results. EGFR SISH amplification studies in archival paraffin-embedded glioblastoma samples showed that SISH can accelerate the diagnostic process in a cost-effective way. Melanoma FISH probes failed to detect a sufficient amount of chromosomal changes necessary for a clinically useful diagnostic tool. Computer based algorithms helped to standardize ISH evaluation. Conclusions. Specific genetic alterations will define new disease entities, requiring ISH as prerequisite to establish the diagnosis. ISH can help to sub-classify morphologically similar neoplasia in terms of therapeutical response and will help to define genetic subgroups within distinct diagnostic groups for treatment purposes. FR-020 Epithelial-mesenchymal transition of non-small cell lung cancer A . Soltermann1 , V . Tischler1 , L . Morra1 , W . Weder2 , H . Moch1 1University of Zurich, Institute of Surgical Pathology, Zurich, Switzerland, 2University Hospital Zurich, Division of Thoracic Surgery, Zurich, Switzerland Aims. Non-small cell lung cancer (NSCLC) is a highly fibrotic malignancy, elaborating a prominent desmoplastic stroma reaction or tumor microenvironment, respectively. Four main modes of carcinoma invasion into its own newly formed stroma are generally recognized: Epithelialmesenchymal transition (EMT), amoeboid, infiltration in cohorts and in collective sheets. We aimed for characterization of the matricellular N-glycoprotein periostin, a major EMT indicator, in the tumor microenvironment of NSCLC. Methods. Malignant pleural effusions from lung adenocarcinoma were screened for N-glycoproteins by shotgun proteomics using liquid chromatography following tandem mass spectrometry (LC-MS/MS). The identified EMT protein periostin was validated on both a tissue microarray of surgically resected patients with NSCLC (n total=532) and on tumor whole sections (n=30) by immunohistochemistry. Isoform-specific PCR following sequencing was performed in frozen specimens. Results. In the pleural effusions, 170 non-redundant N-glycoproteins were identified with high protein probability >0.9, belonging mainly to serum factors and extracellular matrix (ECM) constituents. Periostin was the most robustly identified ECM protein in malignant effusions. On tissue microarrays, strong protein upregulation was predominantly observed at the invasive front in both tumor epithelia and the surrounding extracellular matrix, the so-called matricellular space. In comparison to structural ECM proteins such as collagen, elastin, vimentin and versican, high periostin was found to be most closely associated with clinicopathologic parameters of tumor progression such as higher stage, higher pT and larger size; as well as the squamous cell histotype (all p-values
Abstracts ted genes will in the near future allow for providing helpful information on individual cancer-genomes for individualized tumor therapy. Also, NGS will become applicable to rather small specimen, including biopsies, circulating tumor cells and circulating free DNA in plasma. Even so NGS is already used in the clinical setting, for instance for the detection of disease gene mutations of familial breast and ovarian cancer and for genetic diseases, data analysis and interpretation using biostatistics, bioinformatics, systems biological and mathematical approaches including mathematical modeling is still rather complex. Robust strategies for data analysis are being needed and are being developed. Solving the key problems in cancer biology will therefore only be accomplished by orchestrating a manifold collaboration between different disciplines (life sciences, mathematics, and informatics). Platform comparison will be provided for expression data comparing RNA seq and array based methods. We will glimpse into the future and discuss third generation sequencing and single-molecule sequencing technologies. Important goals are to improve our knowledge on the regulation and function of genes and proteins in single cells, tissue and organs. While NGS is just on its way to be established as a routine diagnostics tool, the next next-gen sequencing techniques are already emerging. Whereas current NGS techniques depend on optics and thus require elaborate signal detection, the third and fourth generation techniques simply measure changes of electric current, either when DNA passes through nanopores or bends nanowires in a sequence dependent manner. Being electronic devices like computer processors, the third and fourth generation sequencing machines will be very fast, very small and rather cheap. FR-023 Prognostoc biomarkers of gastric cancer V . Warneke 1 , H .-M . Behrens 1 , C . Röcken1 , J . Haag1 , K . Balschun1 , C . Böger1 , C . Böger1 , T . Becker2 , J . Hartmann3 , M . Ebert4 , C . Röcken5 1 2 Christian-Albrechts-University, Department of Pathology, Kiel, Christian- Albrechts-University, Department of Surgery, Kiel, 3Christian-Albrechts-Uni versity, Department of Internal Medicine II, Kiel, 4University of Mannheim, Dept . of Medicine II, 5University Hospital Schleswig-Holstein, Campus Kiel, Department of Pathology, Kiel Aims. Chemotherapy for the treatment of gastric cancer (GC) is evolving rapidly and continues to improve patient survival. We studied phenotypic and genotypic biomarkers for GC, in order to test whether these biomarkers are independent prognosticators of patient survival and whether any of these biomarkers should be considered to tailor patient treatment in the future. Methods. 485 patients (299 men, 186 women; median age 68 years) with GC had undergone either total or partial gastrectomy for adenocarcinomas of the stomach or oesophagogastric junction. Survival data and date of death were available for 469 patients. The pTNM-stage was based on surgical pathological examination. The Laurén and mucin phenotype was assessed. H. pylori- and Epstein-Barr virus infections were documented. The following markers were studied: BRAF-, KRAS-, NRAS- and PIK3CA (exon 9 and 20)-genotype, microsatellite instability, Her2/ neu-status, E-cadherin, β-catenin and EpCAM-expression. Results. An intestinal type GC was found in 184 patients, a diffuse type in 224. A persistent H. pylori-infection was found in 64 (15.5%) patients, an EBV-infection in 15 (4.0%). Seventeen (3.6%) GCs showed a KRAS-, 12 (2.5%) a PIK3CA (exon 9)- and 9 (1.8%) a PIK3CA (exon 20)-mutation. No NRAS- and BRAF-mutation was found in our series. 424 (95.1%) GCs were EpCAM- and 46 (10.2%) Her2/neu-positive. 33 (7.3%) GCs were highly microsatellite unstable, 31 (93.9%) of which showed loss of expression of MLH1 and PMS2. Patient survival correlated with Laurén phenotype, MSI-H and BerEP4-expression. Patient age, stage grouping according to the Kiel-proposal, lymph node ratio and Mucin 2 were independent prognosticators of patient survival. 54 | Der Pathologe · Supplement 1 · 2012 Conclusions. A thorough staging and surgical pathological examination is the most important tool to assess patient prognosis. KRAS, PIK3CA (exon 9 and 20), BerEP4-, Her2/neu- and MSI-status may be considered to tailor patient treatment in the future. FR-024 Deep-sequencing: Speed-up diagnostics of colorectal carcinoma M . Rechsteiner1 , A . Bohnert 1 , A . von Teichmann 1 , S . Schmid-Brun1 , P . Schraml1 , H . Moch1 1University Hospital Zurich, Surgical Pathology, Zürich, Switzerland Aims. In colorectal carcinoma, KRAS mutations have emerged as a major predictor of resistance to anti-EGFR antibody treatment. Although the role of BRAF mutations, in predicting the response to anti-EGFR drugs still remains controversial, patients with a mutated BRAF gene exhibit a significant shorter survival than patients without a mutation. In this project we aimed to establish a high-troughput ultra-deep sequencing platform to cope with the increased demand for sequence information at medical institutions. With this platform we intend to unravel low frequency mutations below the detection limit of Sanger sequencing and to elucidate throughput power for diagnostics. Methods. A cohort of 120 patients, diagnosed with colorectal carcinoma, was established. The cohort consisted of 45 patients with KRAS mutations in exons 2 or 3 and 75 patients without a KRAS mutation. This was assessed by Sanger sequencing. The 75 patients with a wild-type KRAS gene were further analysed for BRAF mutations in exon 15 by Sanger sequencing. Results. Fifty ng of genomic DNA isolated from FFPE tissue blocks were found to give reproducible results as input material of the PCR to generate amplicons used for deep-sequencing. The target amplicons were KRAS exons 2 and 3 and BRAF exon 15. The exons 5 to 8 of the p53 gene were also analysed due to high mutation rates in colorectal carcinoma. The amplicons of each patient were labelled with multiplex identifiers (MIDs), and these were shown to be highly specific in the data analysis after deep-sequencing. Seven amplicons of 9 patients were pooled in one single 454 Junior Sequencing run. On average, each amplicon was covered 1000-fold which allowed us to identify mutations at a 4% frequency. Integrated computational down-stream analyses enabled us to speed up the detection and classification of mutations. Results from the first 17 patients yielded 14 mutations located in the p53 gene (82%) and 1 in the BRAF gene (6%). The BRAF mutation was identified as the well known activating mutation V600E. We also included a patient with a known KRAS mutation as control which was successfully verified by deep-sequencing. Conclusions. This newly established method allowed us to analyse 7 amplicons of 9 patients (63 amplicons in total) in one deep-sequencing run within 1 week. The capacity limit of a Junior 454 is 4 runs per week which would allow us to analyse the mutation status for the KRAS, BRAF, and p53 genes of 36 patients with colorectal carcinoma Promotionspreis FR-026 Colocalization algorithms for conversion of traditional immunohistochemistry into virtual multicolor stains A .-S .K . Meyer1 , P . Möller1 , J .K . Lennerz1 1University Ulm, Institute of Pathology, Ulm Aims. Diagnostic immunophenotyping is performed via “mentally” combining single immunohistochemistry (IHC) stains. The discrepancy to research settings, were co-visualization predominates, is due to technical- (i.e. species identity, detection systems) and/or practical hurdles
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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 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 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
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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
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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
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Results. In 18 cases (79%) the caus
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FR-P-168 Autopsy findings in a 2-ye
Page 140 and 141:
FR-P-174 MPGN-like glomerulonephrit
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Poster: Gynäkopathologie und Mamma
Page 144 and 145:
SA-P-011 Genetic aberrations of pre
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Mechanismen, die eine Progression d
Page 148 and 149:
internet server. A network of inter
Page 150 and 151:
Methods. HE-gefärbte Schnittpräpa
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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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