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

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dissection (MBLND) technique to improve the LN staging in gastrointestinal cancers. Moreover, we combined this technique with an ex-vivo sentinel mapping method to further improve the staging. Methods. The technique has been established in pilot studies and than confirmed in prospective and randomized studies. The injections were performed in fresh state. Subserosal or submucosal injection of black ink was performed for the sentinel mapping. Methylene blue (MB) solution was injected afterwards into the main arteries. Results. LN harvest was highly significant improved in the MB groups in comparison to the control groups (colon cancer: 35±18 vs. 17±10; rectal cancer: 30±14 vs. 17±11). MB technique ensured sufficient LN harvest in almost all cases including cases of neoadjuvantly treated rectal cancer. The evSLN detection rate, sensitivity and accuracy in gastric cancer were 87%, 81% and 93%, respectively. Isolated tumor cells were detected after immunohistochemical staining in 3 of 17 cases (18%). The chance to detect a metastasis in an evSLN was 2 times higher in comparison to conventional LNs. In 8% of all cases only evSLN were affected by metastases. Conclusions. MBLND is a highly effective method of improving the LN harvest in gastric cancer. Further application of evSLN mapping is feasible and has the potential to heighten the sensitivity of metastasis detection. SA-004 EBV-assoziierte Tumoren in Interaktion mit dem Immunsystem M . Büttner1 1University Hospital Erlangen, Institute of Pathology, Erlangen Aims. EBV-associated tumours are characterized by a prominent inflammatory infiltrate, which, however, is not able to eliminate the tumour cells. Viral proteins like latent membrane protein 1 (LMP1) can interact with intracellular signalling pathways and thereby modulate the immune reaction. In order to better understand immunological processes in EBV-associated tumours different mechanisms were investigated. Methods. Paraffin embedded material of classical Hodgkin lymphomas (cHL), nasopharyngeal carcinomas (NPC) and gastric carcinomas was investigated by immunohistochemistry and in situ hybridization with regard to the expression of EBV-encoded and cellular genes, which are involved in the regulation of the immune reaction. Cell culture experiments were performed for a better understanding of the mechanisms involved on cellular basis. Results. Hodgkin-Reed-Sternberg (HRS) cells of cHL are B cell derivates with a phenotype which is neither typical for a germinal center B-cell nor of a plasma cell, but rather reminds of an abortive plasma cell phenotype. STAT3 a transcription factor with a central role in the linkage of inflammation and tumorigenesis is expressed in cHL and NPC. LMP1 can induce the chemokines RANTES and MCP-1 in an at least partially NFkappaB- dependent manner. However, those chemokines are predominantly expressed in the inflammatory infiltrate rather than the tumour cells. In EBV-associated cardiac carcinoma an increased number of cytotoxic T cells is found, which might be a sign of an on-going antiviral response. Conclusions. In EBV-associated tumours a complex interaction of cellular and viral factors takes place, which can modulate the intratumoural immune reaction. A better understanding of those processes could help to find potential immune evasive mechanisms applied by the tumours, which could interfere with an effective immunotherapy. Aktuelle Entwicklungen in der Forschung II – Gastrointestinaltrakt SO-001 TNF induces STAT3-mediated inflammation in normal colon epithelial cells S . Chakilam1 , A . Agaimy1 , R . Atreya 2 , M . Gandesiri1 , J . Ivanovska1 , M . Rave- Fränk 3 , H . Christiansen3 , T .T . Rau1 , R . Schneider-Stock 1 1University of Erlangen-Nuremberg, Institute of Pathology, Erlangen, 2University of Erlangen-Nuremberg, Department of Medicine I, Erlangen, 3University Göttingen, Department of Radiation Oncology Aims. Tumor necrosis factor α (TNF) is a pleiotropic cytokine that participates in a wide range of biological activities, including inflammation, growth, differentiation, and apoptosis. TNF is a key molecule in the cytokine network, capable of regulating the expression of other cytokines, such as IL-6 which is known to be a major mediator of inflammation through the activation of the STAT-3 pathway. To simulate the effects of TNF to normal intestine we treated immortalized human colon epithelial cells (HCEC) with 0.66 ng/ml TNF and analyzed the possible TNFmediated functions and signal transduction. Methods. HCEC cells were stimulated for various time points (1, 6, 24, 48 and 72 h). Activation of transcription factors (NF-kB, ATF-2, and STAT3) was assessed by western blotting. Inflammation was detected by real-time RT-PCR and cytokine ELISA. Transcriptional transactivation was measured by EMSA and chromatin immunoprecipitation. Apoptosis was analyzed by Annexin V binding assay and M30 staining. Results. TNF-induced a biphasic pattern of activation of transcription factors NF-kB, ATF-2, and STAT3 with NF-κB and ATF-2 phosphorylation at 1 and 6 h, whereas STAT3 activation (pSTAT3Tyr705) and transcriptional activity was induced later at 48 h. TNF also induced secretion of the pro-inflammatory cytokines IL-6 and IL-8. We assumed that the released IL-6 at early time points causes STAT3 activation. Indeed, IL-6 neutralisation significantly attenuated TNF-induced STAT3 phosphorylation. Moreover, AG490 (JAK inhibitor) pre-treatment decreased TNF-induced STAT3 activation and significantly decreased TNF-augmented IL-6 secretion. As expected, IL-6 stimulation alone also increased pSTAT3Tyr705 levels. In parallel, there was no remarkable apoptosis induction despite an increase in DNA-damage measured by pH2AX foci formation. STAT3 signaling was verified in human tissues from ulcerative colitis patients. Conclusions. These data indicate that HCEC cells seem to develop an inflammatory phenotype upon TNF stress. The TNF-induced inflammation is regulated by IL-6 and STAT3. We hypothesize that the normal mucosa is also actively participating in the development and maintenance of inflammatory conditions in the gut. SO-002 Establishment of a cell culture model to study inflammationassociated oxidative stress as initiator of colorectal neoplasias A . Poehlmann1 , K . Reissig1 , P . Schoenfeld2 , P . Steinberg3 , T . Guenther1 , A . Roessner1 1Otto-von-Guericke University Magdeburg, Department of Pathology, Magdeburg, 2Otto-von-Guericke University Magdeburg, Department of Biochemistry and Cell Biology, Magdeburg, 3Institut of Food Toxicology and Analytical Chemistry, Hannover Aims. Accumulating evidence shows that oxidative stress displayed by reactive oxygen species (ROS) is a major contributor to inflammationassociated cancer. Whether oxidative stress in inflammatory bowel disease (IBD)-associated carcinogenesis is only a promoting factor or linked to tumor initiation is still an open question. To find evidence for the transforming capacity and tumor-initiation effects of ROS, we generated Der Pathologe · Supplement 1 · 2012 | 59
Abstracts a cell culture model. We mimicked ROS exposure of the epithelium in human IBD using the non-tumor human colon epithelial cell line HCEC and H2O2 as ROS. Methods. The clinical course of IBD with multiple recurrences was simulated by repeated H2O2 exposure cycles of the HCEC cell cultures. We generated ten cell lines and confirmed neoplastic transformation by analyzing them for clonal growth, enhanced proliferation, Colony Formation, ROS-release, and β-galactosidase activity. The p53, Kras, and APC mutation status, as well as microsatellite instability (MSI) were assigned. Results. After three treatment cycles with H2O2, HCEC lost cell-cell contact and started pilling up. Surviving HCEC showed uncontrolled proliferation. Anchorage-independent growth in soft agar is often predictive of tumorigenicity in vivo and is considered the most stringent assay for malignant cell transformation in vitro. As ROS-injured HCEC form colonies in soft agar, we concluded HCEC transformation. By checking further hallmarks of cancer, we detected (i) self-sufficiency in growth signals presumably via ROS-induced ROS-release, (ii) a limitless replicative potential by overcoming cellular senescence, and (iii) evading apoptosis. There were no alterations in p53, Kras, and APC gene, or MSI. Conclusions. Our HCEC cell model provides novel insights into tumorinitiating molecular events in IBD-associated carcinogenesis as these cells are more likely to represent the potential target for tumor initiation in vivo. Oxidative stress alone is sufficient to initiate HCEC transformation. Transformed HCEC do not show well-known genetic alterations. We therefore suppose early epigenetic changes to play an important role in the initiation of the IBD-carcinoma pathway. This would further provide the possibility of unravelling novel subsequent genetic alterations that account for tumor initiation. SO-003 Acetone compression and its impact on tumor staging of colorectal cancer J . Kitz1 , A . Gehoff2 , L .-C . Conradi3 , T . Sprenger3 , O . Basten4 , T . Liersch3 , P . Middel2 , J . Rüschoff2 1University Medical Center Göttingen, Department of Pathology, Göttingen, 2 3 Institute of Pathology Nordhessen, Kassel, University Medical Center Göttingen, Department of General and Visceral Surgery, Göttingen, 4Institute of Pathology Marburg, Marburg Aims. Acetone compression (AC; Basten et al. Pathologe 2010) is a method that allows for complete lymph node evaluation in colorectal cancer (CRC), which is particularly important in rectal carcinomas pretreated neoadjuvantly (Gehoff et al. Am J Surg Pathol 2011, accepted). In addition, AC also facilitates detection of any further metastases in mesenteric adipose tissue, e.g. perineural infiltration, which has its own prognostic significance (Poeschl et al. JCO 2010). The present study deals with the significance of AC for tumor staging of colorectal cancer. Not only lymph node status but particularly also the significance of tumor cell deposits and perineural infiltration are discussed. Methods. A total of 245 specimens with CRC were analysed prospectively via AC, half of which were rectal carcinomas. In consecutive cases (10–30 tissue samples each) the following parameters were evaluated: a. AC effect on lymph node size and distribution of metastases in comparison to preceding manual dissection on the same sample; b. The incidence of metastatic spread to lymph nodes and as a tumor deposit or perineural invasion in relation to the tumor location (distal, proximal and at the level of the tumor). Results. In the 245 tested specimens with colorectal cancer, a mean of 30 lymph nodes were assessed. There was no significant difference observed between neoadjuvantly treated or untreated rectal carcinomas. The main effect of AC was seen in lymph node size and metastatic status: In the 10 manually dissected samples, the number of lymph nodes which were
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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
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 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 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
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provided information on survival ti
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Methods. Biopsy specimens from 430
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the OS rate was 53% for patients wi
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FR-P-098 Immunohistological stainin
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FR-P-104 Histopathological evaluati
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within the earliest morphologic det
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Conclusions. In primary imaging a g
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fibrotic neointma development as we
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FR-P-129 Alpha-1-antitrypsin-PiZ-an
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FR-P-136 The expression of central
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cosa and in the periarterial tissue
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FR-P-149 Combination of Castleman d
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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
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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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96. Jahrestagung der Deutschen Gesellschaft für Pathologie e. V ...

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