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

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within the earliest morphologic detectable alterations, i.e. clear cell foci (CCF) of altered hepatocytes. CCF are described in humans indeed, but it is unclear whether these proto-oncogenic pathways are already activated within these foci. Methods. 241 liver resections were examined by using electron microscopy, histology, enzyme- and immunohistochemistry. Results. CCF are present within 35% of the extrafocal tissues of non cirrhotic livers. Electron microscopy illustrates massive glycogen storage within CCF, largely due to reduced activity of the glycogenolytic enzyme glucose-6-phosphatase. Hepatocytes of the CCF overexpress the insulin receptor and the glucose transporter proteins GLUT1 and 4. Insulin induced protooncogenic pathways AKT/mTOR (AKT, chREBP, activated mTOR, inactivated AMPKalpha, activated RPS6, inactivated 4EBP1) and Ras/Raf1 (IRS1, Ras, Raf1, MEK-1, ERK1/2, MKP-3, RALA), enzymes of glycolysis (Glucokinase, PFK, Pyruvate kinase), de novo lipogenesis (ACLY, ACAC, FASN, USP2, AKR1B10, SCD1), beta-oxidation (ACADM) and cholesterol synthesis (HMGCoAR, SQS) are upregulated in the CCF compared to normal liver tissue. Due to activation of these proto-oncogenic factors the proliferation activity in the CCF is 2-fold higher than in extrafocal tissue (Ki67-Index 0.75% vs. 0.36%; p=0.002). Conclusions. CCF reveal a phenotype which is known caused by hyperinsulinism in experimental hepatocarcinogenesis models as well as in human hepatocellular carcinomas. These metabolic changes and activation of proto-oncogenic pathways have not been observed in human CCF so far. Our results indicate that CCF represent precursor lesions of hepatocellular carcinoma also in humans. FR-P-111 Adjuvant fluorescent in situ hybridization in equivocal biliary and pancreatic duct cytology M . Schramm1 , A . Thieme1 , N . Pomjanski1 , H . Neuhaus 2 , A . Böcking1 , S . Biesterfeld1 1Heinrich Heine University, Institute of Pathology, Düsseldorf, 2Evangelical Hospital, Düsseldorf Aims. The information whether a stricture or compression of the biliary and pancreatic ducts is of benign or malignant nature is important for therapy planning. Brushing of the suspect lesion in the context of an endoscopic retrograde cholangiopancreaticography is an established diagnostic procedure with moderate sensitivity and high specificity of conventional cytological diagnosis. Equivocal cytology due to artefacts or insufficient sampling is frequent. The detection of aneusomy by multicolour fluorescent in situ hybridization (FISH) is strongly associated with malignancy. The concern of our study was to determine if the addition of FISH subsequent to the cytological investigation could substantially decrease the number of equivocal cytology diagnoses. Methods. A cohort of 235 biliary/pancreatic duct brushings sent to the Department of Cytopathology during January 2005 and December 2007 was enrolled in this study to determine the diagnostic accuracy of cytology. In a second series of 143 brushings, consisting of all positive specimens (positive control) and all equivocal specimens in the above mentioned period and negative specimens in the period from January to December 2007 (negative control), aneusomy was analysed with the UroVysion FISH multiprobe. A histological and/or clinical follow up according to a reference standard, defined in advance had been available for 219 brushings. Results. In the whole cohort, cytology achieved a sensitivity and specificity of 75.3% and 93.1%, respectively. The reduced specificity, compared with the literature was attributable to the use of cytology as a screening test; all equivocal specimens were assigned as positive for statistics. FISH identified 29 out of 38 (76.3%) evaluable cytologically equivocal specimens as true positive and 9 out of 9 (100%) as true negative, compared to the follow up. All cytological negative (January to December 2007) and 28 out of 29 positive specimens were confirmed by FISH. Aneusomy was not observed in benign lesions, according to follow up data. Conclusions. Adjuvant analysis of aneusomy with multicolour FISH in biliary/pancreatic duct brushings reduces equivocal cytology rate to a great extent and is 100% specific. Poster: Herz- und Gefäßpathologie FR-P-112 The impact of genetic inactivation of the LIM-ony-protein FHL2 on cardiac remodelling D . Goltz1 , E . Ramadori1 , S . Huss2 , M . Besmens3 , R . Meyer4 , R . Büttner2 1 2 University of Bonn, Dept . of Pathology, Bonn, University of Cologne, Dept . of Pathology, Köln, 3University of Bonn, Physiology II, Bonn, 4University of Bonn, Physiology II, Bonn Aims. LIM-domain containing proteins play a decisive role during ontogenesis and cellular differentiation. The LIM-only protein Fhl2 associates with cytoplasmatic scaffolding proteins and acts intranuclearly as a co-activator and co-repressor of transcription factors. Fhl2 is specifically expressed within the cardiovascular system during ontogenesis and high expression levels continue throughout lifetime. This suggests that Fhl2 is also of importance during cardiovascular remodelling. Fhl2 deficiency is known to induce an exacerbated cardiac hypertrophy upon chronic beta- adrenergic stimulation. This study investigates cardiac remodelling in the Fhl2 deficient organism caused by an increase in cardiac afterload. Methods. Experimental transverse aortic constriction (TAC) was induced in control animals and Fhl2-/- mice. After 14 days, morphometric and hemodynamic evaluations using a Millar catheter were performed. Vascular contraction and relaxation was examined using a Mulvany myograph and renal renin-mRNA-expression was analysed by quantitative real time PCR. Cardiac fibrosis was addressed by histologic techniques. Results. TAC induced a rise in pre-stenotic diastolic arterial blood pressure and a significantly more severe increase in pre-stenotic systolic arterial blood pressure in the Fhl2-/- animal compared to the control animal. The transstenotic pressure gradient, however, was identical in the Fhl2- /- animal and the control animal. In vitro vascular contraction measurements proved that aortic rings of Fhl2 deficient mice featured combined contractile dysfunction and disturbed relaxation that was independent of receptor mediation. As a consequence, renal renin-mRNA-expression was significantly suppressed in Fhl2-/- mice. Cardiac hypertrophy, however, was less distinct in Fhl2 deficient animals than in wild type animals as was cardiac fibrosis. Conclusions. Fhl2 deficiency encompasses cardiac protection against chronic increases in cardiac afterload, in this context due to a suppression of the renin angiotensin axis. FR-P-113 The impact of Crp2 deficiency on cardiovascular adaptation and remodelling D . Goltz1 , E . Ramadori1 , S . Huss2 , R . Meyer3 , R . Büttner2 1 2 University of Bonn, Dept . of Pathology, Bonn, University of Cologne, Dept . of Pathology, Köln, 3University of Bonn, Physiology II, Bonn Aims. Lim domain containing proteins among them Crp2 play a central role in organogenesis and cellular differentiation. Crp2 is specifically expressed in cardiovascular tissue. Its up-regulation in cardiomyocytes coincides with vascular smooth muscle differentiation in vitro. We investigated the vascular phenotype of Crp2 deficient mice in vitro and addressed the issue of cardiac remodelling under chronic elevation of left ventricular afterload in vivo. Der Pathologe · Supplement 1 · 2012 | 119
Abstracts Methods. Phenylephrine and potassium induced vascular contraction and endothelially mediated relaxation was investigated in Crp2 deficient mice and control animals by using the Mulvany Myograph. Transverse aortic stenosis (TAC) was induced in Crp2-/- mice and wild type animals. After 14 days, cardiac function was evaluated by cardiac catheterisation using a Millar catheter. Cardiac hypertrophy and fibrosis was addressed my morphometric analysis. Results. Aortic rings of Crp2 deficient animals displayed an isolated contractile disorder. Vascular contraction was enhanced both under stimulation with phenylephrine and under increased extracellular potassium concentrations. Endothelially mediated relaxation was unaffected by Crp2 deficiency. 14 days after TAC Crp2-/- animals developed exacerbated cardiac hypertrophy and moderate myocardial fibrosis compared to the control group. We observed a significantly more severe elevation of blood pressure levels in Crp2-/- animals compared to the control group. At the same time the pressure gradient across the stenosis was unchanged in wild type and Crp2-/- animals. Functional analysis of cardiac contraction revealed an acute diastolic dysfunction and reduced contractile reserve in Crp2 deficient mice. Conclusions. Crp2 deficiency leads to an aggravated vascular contraction upon both receptor mediated and receptor independent stimuli in vitro. In vivo, TAC induces an exacerbated cardiac hypertrophy in Crp2-/- animals. Crp2 plays a central role in cardiac and vascular homoeostasis, its loss leads to disturbed cardiac remodelling. FR-P-114 Functional dichotomy of myofibroblasts in chronic cardiac diseases M . Franz1 , A . Renner2 , M . Ditze3 , K . Grün4 , D . Neri5 , H . Kosmehl6 , H .R . Figulla1 , I . Petersen3 , A . Berndt3 1University Hospital Jena, Department of Internal Medicine I, Jena, 2Ruhr- University of Bochum, Heart Center North Rhine-Westphalia,, Bad Oeynhausen, 3University Hospital Jena, Institute of Pathology, Jena, 4Uni versity Hospital Jena, Department of Cardiothoracic Surgery, Jena, 5Swiss Federal Institute of Technology, Institute of Pharmaceutical Sciences, Zürich, Switzerland, 6HELIOS-Klinikum Erfurt, Institute of Pathology, Erfurt Aims. Chronic rejection following heart transplantation is accompanied by allograft vasculopathy (CAV) and fibrosis (CIF) and represents a valuable model for the cardiac remodelling during ischemia. Processes are accompanied by extracellular matrix remodelling and the recruitment of myofibroblasts (MyoFb). ED-A+ fibronectin was recently suggested as a co-regulator of MyoFb development. The functional role of MyoFb in the context of hypoxic damage is not fully understood up to now. Aim of the study was to analyse the relation of MyoFb to the grade of chronic rejection and to ED-A+ fibronectin deposition in a rat heart transplantation model. Furthermore, the influence of the MyoFb secretom on cardiac myocytes under hypoxic conditions was investigated in vitro. Methods. A model of chronic rejection after rat heart transplantation (rHTX) was used. Allografts, recipient and control hearts were subjected to histological assessment of rejection grade and to immunofluorescence co-localization analysis of ED-A+ Fn and alpha-SMA. For in vitro investigations, HL-1 cells were used as a model for cardiomyocytes and the hTERT-BJ1 fibroblasts cell line was as a model for fibroblasts. alpha-SMA positive myofibroblasts were generated by stimulation with transforming growth factor-beta 1 (TGF-beta 1. Hypoxia in HL-1 cells was simulated by cultivation in presence of deoxyglucose. HL-1 cells were incubated with unconditioned medium and Fb or MyoFb supernatant. LDH as well as Troponin-I levels were measured in the supernatant by ELISA. Results. In the rHTX model the grade of chronic rejection showed a clear association to the amount of alpha-SMA positive cells. Extensive codepositions of ED-A+ Fn and alpha-SMA occurred in CAV and also in fibrosis. TGF-beta 1 treated hTERT-BJ1 fibroblasts showed a substantial increase in alpha-SMA and were therefore designated as MyoFbs. Pre- 120 | Der Pathologe · Supplement 1 · 2012 culturing of HL-1 in MyoFb-conditioned medium resulted in a protection against deoxyclucose caused cell damage. Conclusions. The process of chronic rejection accompanied by tissue hypoxia entails MyoFb activation and associated ED-A+ fibronectin deposition speaking well for a perpetuating process. alpha-SMA is suggested as a valuable marker to detect and quantify tissue remodelling in CAV and fibrosis. A protective effect of MyoFb on myocytes under hypoxic stress could be evidenced in vitro. With respect to this result, MyoFb based diagnostic and therapeutic approaches for ischaemic heart failure should consider this dichotomy. FR-P-115 Tumours of the heart, great vessels and mediastinum: a retrospective study H . Al-Mohamed1 , R . Hetzer1 , K . Wassilew1 1Deutsches Herzzentrum Berlin Aims. Primary cardiac and pericardial tumours are rare, with a prevalence ranging from 0.001–0.3%. A retrospective study was conducted with the focus on epidemiology and pathological features of cardial, pericardial and mediastinal tumours. Additionally, the results were compared to those of already existing similar studies. Methods. In a review of all pathological records of our institution from 2000 to 2010 268 cardial, pericardial and mediastinal tumours were identified. Results. The majority of cases (n=209, 78%) were benign neoplasms, myxomas being the most frequent histological type (n=105, 50.24%). Among the primary malignant tumours (n=59, 22.01%), sarcomas (n=18), carcinomas (n=10) and tumours of the haematopoietic system (n=9) were the most frequent. Conclusions. This study gives an overview of primary and secondary neoplasms in the heart, great vessels and mediastinum, with their preferential localizations and their epidemiological distributions. As found by other studies, myxoma is the most common tumour. FR-P-116 Pitfalls treating tumors close to carotid artery bifurcation – a case report H .P . Kuhne1 , M . Hegenscheid1 , E . Fietze2 , A . Lieber1 1 2 Hospital of the Armed Forces Germany, Berlin, Clinic for Pathology Berlin, Berlin Aims. A 55-year-old patient presented with neuralgia pain in area of right face for further diagnostic and therapy. He reported about an operation in the region of lateral neck in his youth with no further information. There was no tumor palpable, no local pain. Beside this patient is deaf since birth and suffers of a gynecomastia with hyperprolactinemia treated with Cabergolin at the moment. An MRI of brain and skull was without pathological findings. Methods. An MRI in the region of right bifurcation of carotid artery showed a tumor with diameter 1.8×2.7×3.6 cm suspected to be a so called glomus tumor. In a color duplex sonography there was seen a normal flow, also a normal MRI of brain and supraaortic vessels was done. During operation we could identify the tumor beginning at the vagus nerve. We did a complete resection in toto macroscopical, an instantaneous section showed no signs of malignancy. Results. Histological result showed a ganglioneuroma with regressive changes. Tumorspread was into a cleft transection. Most cells showed in an immunohistology coloration strong expression of S-100 proteine and very few strongly regressive changed gangliocytes, furthermore with grained expression of Synaptophysin and marginal CD-56. After inconspicuous healing process patient was presented in a interdisciplinary tumor board where no further need of surgery was decided.
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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
Page 42 and 43:
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
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
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 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
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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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