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

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DO-062 Tumor-associated macrophages in pediatric classical Hodgkin lymphoma: associations with Epstein-Barr virus, lymphocyte subsets and prognostic impact M . Barros 1 , R . Hassan 2 , G . Niedobitek 1 1 Unfallkrankenhaus Berlin, Institut für Pathologie, Berlin, 2 Brazilian National Cancer Institute, Bone Marrow Transplantation Center, Rio de Janeiro, Brazil Aims. The number and type of tumor-associated macrophages are implicated in the biology of classical Hodgkin lymphoma (cHL) in adults. Due to the immunological differences between children and adults, and to the cross-talk between innate and adaptive immune system, it is hypothesized that number, function and prognostic impact of macrophages in pediatric cHL may be different from adult cases. Methods. We analyzed the number of macrophages and dendritic cells (DCs) in the tumor microenvironment of pediatric cHL by immunohistochemistry (IHC) and image analysis system. Epstein-Barr virus (EBV) status was determined by EBER-specific in situ hybridization and IHC. Results were analyzed in the context of age group, histological characteristics and clinical follow-up. Results. The younger ages were characterized by a more intense CD14+ and CD163+ cell infiltrate (p=0.01 and p=0.025, respectively). In relation to nodular sclerosis, mixed cellularity subtype was characterized by high number of CD14+, (p=0.003) and CD163+ cells (p=0.027). EBV+ cases exhibited higher numbers of CD14+ (p
Abstracts Methods. Three ALK + ALCL cell lines were transduced with C/EBPβ shRNA by lentiviral gene transfer. The C/EBPβ knockdown was quantified by RT-qPCR and Western Blot. MiRNA expression in ALK+ ALCL cell lines with and without C/EBPβ knockdown, ALK − ALCL cells and T-cells were analyzed by deep-sequencing, to determine differentially regulated and expressed miRNAs in ALK+ ALCL. The influence of C/ EBPβ on the expression of miRNA candidates and the differential expression in ALK+ ALCL was validated by RT-qPCR in cell lines and in primary tumors. Results. Next-generation sequencing analysis resulted in 80 significantly regulated miRNAs after C/EBPβ knockdown in the three ALK+ ALCL cell lines. Three of these miRNAs (miR-181a*, miR-146b-5p, miR-203) were significantly regulated in all three cell lines. The C/EBPβ dependent regulation of these miRNAs was confirmed in two cell lines by RTqPCR. Comparison of the results of the ALK+ ALCL cell line SUDHL-1 and T-cells or SUDHL-1 and the ALK− ALCL cell line revealed 379 or 301 significantly regulated miRNAs respectively. ALK− ALCL cells and T-cells showed a significant difference in the expression levels of 366 miRNAs. A hundredfold change in expression levels was observed for a few interesting miRNAs of the different signatures. The differential expression of some of the most remarkable miRNAs in ALK+ ALCL was validated in primary human ALK+ and ALK− ALCLs by RT-qPCR. Several of these miRNAs play important roles in diverse cancers with tumor-suppressing or oncogenic functions. Conclusions. Three miRNAs were found to be regulated by C/EBPβ in two ALK+ ALCL cell lines. Numerous miRNAs are differentially expressed in ALK+ or ALK− ALCL cells and T-cells. Several miRNAs which are significant differentially expressed in ALK+ and ALK− ALCLs separate ALCLs depending on their ALK status. We identified a miRNA profile specific to ALK+ ALCLs. DO-066 The role of C/EBPβ in the phenotype of ALK+ anaplastic large cell lymphoma J .-A . Schmidt 1 , I . Bonzheim1 , S . Schäfer1 , F . Fend1 , L . Quintanilla-Martinez1 1University Hospital Tübingen, Institute of Pathology and Neuropathology, Tübingen Aims. ALK+ anaplastic large cell lymphoma is characterized by the loss of pan T-cell antigens and the unusual expression of myelomonocytic surface markers. The forced overexpression of the transcription factor C/ EBPβ in B and T-cells has been shown to induce transdifferentiation into macrophages. Since C/EBPβ has been shown to play a central role in the pathogenesis of ALK+ ALCL, the aim of the study was to investigate its influence on the unusual phenotype of ALK+ ALCL. Methods. The expression of 242 surface antigens was investigated in ALK+ ALCL cell lines before and after the specific knockdown of C/ EBPβ using the BD Lyoplate Human Cell Surface Marker Screening Panel by flow cytometry. A highly specific C/EBPβ-shRNA was transduced by lentiviral infection. The expression of significant surface markers was validated by immunohistochemistry and Western blot in primary ALK+ and ALK− ALCL cases. Results. The surface marker screening confirmed the loss of T-cell specific markers, such as TCR chains and CD3, and overexpression of EMA and activation markers CD25 and CD30 but did not support the unusual expression of myeloid markers as CD13 or CD33, as previously described. Activation surface markers, including CD25, CD30, CD97 and CD98, showed downregulation after C/EBPβ knockdown indicating a role for C/EBPβ in the activation of ALK + ALCL cells. CD147 (EMMPRIN) was strongly expressed in ALK + ALCL cells, and was downregulated after C/ EBPβ knockdown. Interestingly, CD147 was differentially expressed in ALK + ALCL when compared to ALK − ALCL primary cases. Conclusions. Surface marker screening in ALK+ ALCL revealed an influence of C/EBPβ on the activation phenotype of the neoplastic T-cells and expression of CD147, an inductor of matrix metalloproteinases implica- 32 | Der Pathologe · Supplement 1 · 2012 ted in tumor progression and metastasis in solid tumors. The differential expression of CD147 in ALK + ALCL suggests its involvement in the pathogenesis of ALK + ALCL. AG Orthopädische Pathologie DO-079 Histomorphological and clinical characterisation of Epstein-Barr virus-associated post-transplant smooth muscle tumours L . Maegel1 , J . Rische1 , C . Tiede1 , J . Salem1 , F . Laenger1 , H . Kreipe1 , K . Hussein1 , D . Jonigk1 1Hannover Medical School, Institute of Pathology, Hannover Aims. Histomorphological and clinical characterisation of Epstein-Barr virus-associated post-transplant smooth muscle tumours. Methods. Own cohort: Five PTSMT were examined by histology, immunohistochemistry and molecular methods [mean age of patients 10 years; PTSMT developed after a mean interval of 44 months following liver (n=2), heart (n=2) or bone marrow (n=1) transplantation]. Metadata analysis: Data of 64 PTSMT cases (including our cohort) of the last 20 years were re-evaluated by applying survival analysis. Molecular analyses: All specimen of our cohort underwent compartment-specific laser microdissection and processed for further quantitative real-time PCR analysis. Gene expression of transcripts for a set of 20 EBV-associated endogenous human genes were analysed by qPCR: transcription factors MYC, TP53, NFKB1; apoptosis factors such as BAX; JAK3/STAT signal factors; cytokines such as VEGF; miR-155 and miR-146a. To evaluate the origin of PTSMT – either from the recipient or from the donor – short tandem repeat (STR)-PCR was performed (“molecular fingerprinting”). Results. Histomorphology and immunoprofile (total cohort, n=64): – Spindle shaped, leiomyogenous cells (actin+/desmin+/EBER+), local invasion. – Most PTSMT show no marked cellular atypia, no tumour necrosis,
Page 2 and 3: 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 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 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
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differentiated and TNM stage III or
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pressed moderate levels of the prot
Page 96 and 97:
FR-P-037 MALDI imaging reveals COX7
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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
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aims are twofold: 1) to verify the
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Results. Her2/neu status in TMAs an
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prognostic impact was found in rect
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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
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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
Page 126 and 127:
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
Page 140 and 141:
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
Page 160 and 161:
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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