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

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and desmoplastic reaction are different. SNAIT revealed more cohesiveness and lower vascular spreading than CRAIT. CXDX2 and CK20 expressions are identically. CK7 and Synaptophysin demonstrated no reliable differences, even though SNAIT are more often positive as CRAIT. Mutations analyses exhibited for 30 SNAIT negative results for EGFR. One case (1/30) only was positive for K-RAS Mutation (Mut g/g 12 Asp.) and only one case for b-rafV600E, whereas about 60% of cases revealed a p53 expression mostly in Exon 5, thrice in Exon 8/9. Conclusions. Subtile studies detect dissimilarities of CRAIT and SNAIT. However, if in a given case the discrimination is problematic, the molecular status can be helpful. Molecular results reflect the different pathway of these similar tumors. Hence it follows, that a morphologic mimicry does not imply biologic relatedness! SA-P-044 The G protein coupled-receptor GPR81 is upregulated in colorectal carcinomas with KRAS wild type genotype A .-K . Wenke1 , K . Balschun1 , C . Röcken1 1Christian-Albrechts-University Kiel, Department of Pathology, Kiel Aims. The KRAS genotype is essential for the response to a targeted therapy in advanced colorectal carcinoma (CRC). Several studies revealed that only patients with wild type KRAS (KRASwt) benefit from a therapy with monoclonal antibodies like cetuximab (Erbitux®) and panitumumab (Vectibix®) which block the intracellular cascade following activation of the epidermal-growth-factor-receptor (EGFR). Therefore, the identification of new therapeutic targets is very important. G protein coupled-receptors (GPCRs) are interesting candidates, since they are known to transactivate the EGFR signaling pathway. The aim of this study was the identification and functional analysis of GPCRs which are differentially expressed in colorectal carcinoma dependent on KRAS genotype. Methods. mRNA expression of KRASwt tumor and non-tumor tissue of eight patients was compared to eight cases with KRASmut tumor and non-tumor tissue using Affymetrix GeneChip® Human Gene 1.1 ST Arrays. Differential gene expression of interesting candidate genes was validated by quantitative RT-PCR and immunohistochemical staining of a validation series of 46 colorectal carcinomas (28 KRASwt, 18 KRASmut tumors). Results. We found 32 differentially regulated GPCRs comparing gene expression of normal and tumor colon tissue. An increased expression of GPR81, NIACR1, NIACR2, GPR143, HTR1D and LGR5 in carcinoma tissue could be confirmed. However, GPR81 is the only receptor being significantly differentially regulated according to the KRAS genotype of the tumor. Conclusions. Our expression analyses demonstrate a correlation of GPR81 expression with the KRAS genotype in CRC. The functional role of GPR81 in colorectal carcinogenesis has to be analyzed in further studies. Additionally, a comprehensive expression analysis on an enlarged patient series of 2000 cases will show if GPR81 could serve as a proper therapeutic target or a potential prognostic marker for colorectal carcinoma. SA-P-045 Polysomy and amplification status of EGFR in primary colorectal cancer and in matched metastases C . Giedl1 , A . Kiesl1 , F . Hofstädter1 , W . Dietmaier1 1University of Regensburg, Institute of Pathology, Regensburg Aims. There is a need for predictive biomarkers that identify patients most likely to respond to targeted treatment. EGFR is an important target for therapies using monoclonal antibodies and tyrosine kinase inhibitors (TKIs). We analyzed the polysomy and amplification status of EGFR in primary colorectal cancers, matched metastases, and looked if differences in the polysomy and amplification status exist which could influence targeted therapies. Methods. 54 primary colorectal cancers and 94 metastases of primary colorectal cancers were analyzed. The EGFR gene copy number was evaluated by fluorescence in situ hybridization (FISH). Specimens that have >40% of cells displaying ≥4 copies of the EGFR signal and specimens that showed an EGFR to CEP7 ratio ≥2 over all scored nuclei were counted as EGFR FISH-positive. Also specimens with gene clusters (≥4 spots) in ≥10% of tumor cells and specimens with at least 15 copies of the EGFR signals in ≥10% of tumor cells were counted as EGFR FISH-positive. Results. A high EGFR polysomy was found in 18 of the 54 primary colorectal cancers (33.3%) and in 30 of the 94 evaluated syn-or metachronous metastases in lymph nodes, liver, lung, ovary, peritoneum, skin, brain, urinary bladder and bone (31.9%). In contrast no real gene clusters and real EGFR amplifications were found. 18 of 22 matched metastases from EGFR FISH-positive primary colorectal cancers were also EGFR FISHpositive (81.8%) showing a high accordance but no complete congruence. In addition, 1 case showed an EGFR FISH-negative primary colorectal cancer and a EGFR FISH-positive metastasis. Conclusions. The discrepancy of EGFR polysomy and amplification status found in primary colorectal cancers and matched metastases demonstrate a tumor-metastases diversity, which should be considered in patients’ treatment regime. SA-P-046 Detection of KRAS and BRAF mutation in Chinese colorectal carcinoma patients by pyrosequencing M . Ye1 , J . Chen1 , M . Lai1 1Zhejiang University, School of Medicine, Hangzhou, China Aims. KRAS and BRAF mutation status were reported to be a possible biomarker which response to EGFR antibody chemotherapy in colorectal carcinoma. Recently, pyrosequencing is proved as a powerful and convenient method for KRAS and BRAF mutation detection by a lot of groups in the U. S. and Europe. In China, there are rare labs or groups to setting up pyrosequencing method for molecular clinical diagnosis. Methods. 180 FFPE CRC tissue samples were microdissected to obtain the tumor cells and remove the stroma contents, then the genomic DNA was extracted from these samples by routine method. A pyrosequencing assay based on PCR was designed to characterize KRAS codon 12, 13 and BRAF codon 600 mutation status by Pyromark Q24. The SW620 and HT29 CRC cell lines were used as controls in pyrosequencing. Results. Mutation status of KRAS codon 12 was identified in 65/180 (36.11%) samples, among them,1 sample was 34G>A mutation(0.56%), 2 samples were 34G>C mutation(1.11%) , 2 samples were 34G>T mutation (1.11%), 29 samples were 35G>A mutation (16.11%), 1 was 35G>C mutation (0.56%) and 30 were 35G>T mutation (16.67%). 20 samples were mutant for KRAS codon 13 (11.11%)with the nucleotide change 38G>A for 19 samples (10.56%) and 1 for 38G>A (0.56%). 16/180 tumors harbored a mutation of 1799T>A in BRAF codon 600 mutation (8.89%). Conclusions. The KRAS and BRAF mutant frequencies of the 180 FFPE tissue samples are generally consistent with those recently reported. Although the amount of samples was limited, more CRC patients are needed to be detected in the year future. Der Pathologe · Supplement 1 · 2012 | 153
Abstracts SA-P-047 Alternative splicing of Daxx-beta is reduced in renal cell and colorectal carcinoma S . Funke 1 , N . Wethkamp 1 , S . Heikaus 1 , K .L . Schäfer 1 , H .E . Gabbert 1 , C . Mahotka 1 1 University Hospital Düsseldorf, Düsseldorf Aims. Death associated protein (Daxx) is an important transcriptional co-repressor for a large number of genes, mostly related to apoptosis. Daxx interacts with p53 and represses its transcriptional activity. Alternative splicing of the Daxx results in the generation of a c-terminally truncated and modified isoform termed Daxx-beta. As we shown before, the new C-terminus leads to a markedly reduced affinity of Daxx-beta to PML and p53. Consequently, Daxx-beta is unable to repress transcriptional activity of p53. Because deregulation of p53 is closely related to carcinogenesis, alternative splicing of Daxx may also participate in tumour development and progression. Here, we examined the in vivo splicing pattern of Daxx-beta during renal and colon carcinoma progression. Methods. Semi-quantitative real-time PCR were performed with flash frozen resected tissue of 43 renal cell carcinomas (RCCs) of the clear cell type and 40 colorectal carcinomas (CCs) from different tumour stages as well as 49 and 38 samples from the corresponding non-neoplastic kidney and colon epithelia, respectively. Results. Statistical calculation revealed a significant reduction of Daxxbeta isoform in both tumour entities compared to the corresponding non-neoplastic tissue. These alterations were detected already at early tumour stages (pT1+pT2) and did not further change in late stages (pT3+pT4). Conclusions. Our results indicate for the first time that splicing of Daxxbeta is reduced in all tumour stages of renal cell and colorectal carcinoma, and that Daxx-beta could be a potential candidate for a new biomarker on transcript level. SA-P-048 Modulation of Wnt and Hedgehog signaling pathways is linked to retinoic acid-induced amelioration of chronic fibrosing inflammation P .J . Nelson1 , S . Porubsky2 , C . von Toerne1 , J . Bedke2 , S . Safi2 , N . Gretz2 , H .-J . Gröne2 1 2 University of Munich, München, German Cancer Research Center, DKFZ, Heidelberg Aims. Chronic renal allograft damage (CAD) is manifested by a smoldering inflammatory process that leads to transplant glomerulopathy, diffuse interstitial fibrosis and tubular atrophy with loss of tubular structures. Methods. Gene expression pathway analysis was used to detect new inducers of fibrosis. Using a Fischer 344 (RT1lvl) to Lewis (RT1l) rat renal allograft model, transcriptomic profiling and pathway mapping, we have previously shown that dynamic dysregulation of the Wnt signaling pathways may underlie progressive CAD. Retinoic acid, an important regulator of differentiation during vertebrate embryogenesis, can moderate the damage observed in this experimental model of CAD. Results. We show here that subsets of the Hedgehog (Hh) and canonical Wnt signaling pathways are linked to the pathophysiology of progressive fibrosis, loss of cilia in epithelia and chronic dysfunction. Oral treatment with 13cis retinoic acid (13cRA) was found to selectively ameliorate the dysregulation of the Hh and canonical Wnt pathways associated with CAD, and lead to a general preservation of cilial structures. Conclusions. Interplay between these pathways helps explain the therapeutic effects of retinoic acid treatment in fibrosing inflammation, and suggests future targets for moderating chronic fibrosing organ damage. 154 | Der Pathologe · Supplement 1 · 2012 SA-P-049 Multiciplicity in sporadic inflammatory fibroid polyps and GISTs implicating a field effect S . Huss1 , H . Löser1 , E . Kleimann2 , S . Eidt3 , R . Budde4 , W . Weichert5 , A . Szöke6 , C . Röcken7 , A . Hölscher8 , W . Hartmann1 , S . Merkelbach-Bruse1 , H .-U . Schildhaus1 , R . Buettner1 , E . Wardelmann1 1 2 University Hospital Cologne, Institute of Pathology, Köln, St . Franziskus Hospital, Cologne, Department of Surgery, 3St . Elisabeth-Krankenhaus Köln Hohenlind, Institute of Pathology, Köln, 4Institute of Pathology in Cologne – St . Vinzenz-Hospital, 5University Hospital Heidelberg, Institute of Pathology, 6 7 Institute of Pathology, Cologne – Deuz, Christian-Albrechts-University, Kiel, Institute of Pathology, 8University Hospital Cologne, Department of Surgery Aims. Inflammatory fibroid polyps (IFPs) are rare benign and mesenchymal tumors. Activating PDGFRA mutations play a central role in the pathogenesis of IFPs and have been shown to be a key player in a subset of gastrointestinal stromal tumors (GISTs). Whereas in GIST PDGFRA mutations are considered to transform one of the subtypes of precursor cells of interstitial cells of Cajal, in IFP an hitherto not further identified mesenchymal progenitor cell type of the submucosa is mutated and develops towards a tumour. Methods. The vast majority of IFPs occur as solitary tumors. Here, we report on molecular and clinicopathologic features of three patients presenting with multiple IPFs and syn- or metachronous GISTs. Results. The first case had multiple IFPs in a duodenal segment and developed a metachronous gastric GIST. Both tumors (IFPs and GIST) revealed exactly the same somatic PDGFRA exon 12 mutation (p.Y555C). The same observation of an identical PDGFRA exon 18 mutation (p.D842V) in both a gastric GIST and multiple IFPs in the duodenum was made in a second case. In the third case, multiple IFPs were found in a jejunal segment, all carrying the same somatic substitution mutation in exon 18 of PDGFRA (p.[R841K(+)D842I]). Conclusions. The coincidence of exactly the same sporadic PDGFRA mutation in multiple IPFs and syn- or metachronous GISTs points at closely interrelated precursor cells driving both neoplastic processes. With respect to sporadic multiciplicity, our data suggest a field effect contributing to the pathogenesis of such IFPs and GISTs. SA-P-050 Quantitative PCR analysis for detection of cmV infection in patients suffering from ulcerative colitis using FFPE material N . Wethkamp1 , C . Bersch1 , H .-W . Kohlmann2 , V . Meister3 , M . Respondek1 1 2 Institute of pathology, Dr . Respondek, Vechta, Praxis f . Pathologie, Respondek, Vechta, 3St . Marien-Hospital, Gastroenterology, Vechta Aims. Several lines of evidence indicate that cmV infection can be substantially associated with the onset of ulcerative colitis, especially in immunocompromised patients. In order to estimate the impact of cmV infection and monitoring efficacy of antiviral treatment a real-time PCR Assay was developed to quantify cmV viral load in gastric tissue samples. Methods. DNA-samples derived from FFPE material of patients with ulcerative colitis were quantitatively analysed for cmV infection by Taq- Man technology. Via two independent PCR reactions cmV DNA and human GAPDH copy numbers were quantified, using a plasmid coding for both target sequences as an external standard. Finally, viral load in the analysed tissue was expressed as cmV copy numbers per 100,000 cells (as calculated by the obtained GAPDH copy numbers). Results. A total of 89 samples from 22 patients were evaluated for cmV infection while varying section numbers (ranging from 1–12) were analysed per patient. In 29 samples (32%) referring to 50% of the patients cmV DNA could be detected. Here, three patients (27%) showed a viral load of
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Inhalt Der Pathologe · Supplement
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Inhalt Der Pathologe · Supplement
Page 6 and 7:
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
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
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 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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