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

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Pancreatic Adenocarcinoma SG-137 Serum MiR-192 and MiR-194 as tumor biomarker for pancreatic ductal adenocarcinoma J . Zhang 1 , C .-y . Zhao 1 , D .-h . Yu 1 , Y . Chen 1 , Q .-h . Liu 1 , M . Shi 1 , J .-t . Zhang 1 , G . Jin 1 , P . Cheng 1 , X .-g . Hu 1 , C .-r . Ni 1 , M .-h . Zhu 1 1 Department of Pathology, Changhai Hospital, Shanghai, China Aims. To assess the validity of using serum miRNA signatures of PDAC as biomarkers for diagnosis. Methods. MiRNA microarray was used to detect the differences between PDAC samples and normal pancreatic tissues. MiR-192 and miR-194 were found in the tissues of human PDAC and in the explants in tumorbearing SCID mice by locked nucleic acid-based in situ hybridization (LNA-ISH). Serum levels of miR-192 and miR-194 in PDAC patients, duodenal adenocarcinoma patients and healthy controls, as well as six pancreatic cancer cell lines and their culture supernatants were determined by real-time PCR. Results. Eight miRNAs were found overexpressed and eight were lowly expressed in PDAC tissues compared with those in the normal pancreatic tissues. MiR-192 and miR-194 were found overexpressed in the tissues of human PDAC and in the explants in tumor-bearing SCID mice. The levels of miR-192 and miR-194 in the supernatants of six pancreatic cancer cell lines were positively correlated with their cellular expressions (r=0.849, p
Abstracts SG-140 Sialinomycin induces autophagic and apoptotic cell death in pancreatic carcinoma cell lines M . Vogt 1 , B . Verdoodt 1 , S .-T . Liffers 1 , A . Tannapfel 1 , A . Mirmohammadsadegh 1 1 Ruhr-University of Bochum, Institute of Pathology, Bochum Aims. Salinomycin a polyether antibiotic, is produced by a strain of streptomyces albus and has anti-microbial and anti-coccodial activities. Recently, a number of studies described anti-tumor properties of salinomycin, in particular its effect on chemoresistant tumor initiating cells. In the present study, we investigated the impact of salinomycin mediated activation of MEK/ERK signalling pathway on autophagy and apoptotic cell death in pancreatic cancer cell lines. Methods. Two pancreatic cell lines MIAPaCa-2 and PaTu8902 were used to analyze the effect of salinomycin on cell viability, autophagy and apoptosis. The effect of salinomycin on autophgay was investigated by transmission electron microscopy (TEM) for detection of autophagic vesicles and processing of LC3B, microtubule-associated protein 1 light chain 3 isoform B (LC3B). Towards investigating the role of salinomycin on apoptotic cell death we used caspase3/7, FACS, Western blot analysis and immunofluorescence staining. Results. Salinomycin treatment inhibits cell viability and colony forming in MIA PaCa-2 and PaTu8902 in a time and concentration depending manner. In both cell lines salinomycin was able to induce autophagic cell death, detected by LC3 processing and formation of autophagic vacoules. Salinomycin was able to induce autophagic and apoptotic cell death in MIAPaCa-2 cell lines. In MIAPaCa-2 cells the salinomycin induced autophagic cell death was dependent on ERK1/2 pathway. In contrast, salinomycin induced autophagic cell death in PaTu8902 was independent of ERK1/2. Conclusions. Salinomycin, a novel anti-tumor drug is able to induce autophagic and apoptotic cell death depending on cellular background. Mammary Cancer SG-141 Kindlin2 up-regulation promotes tumor progression W . Fang1 , T . Zhao1 , H .-q . Zhang2 1Department of Pathology, Key Laboratory of Carcinogenesis and Translational Research, Beijing, China, 2Peking University Health Science Center, Beijing, China Aims. Kindlin-2 has been confirmed as an essential element of bidirectional integrin signaling. In recent years, the relationship between Kindlin-2 expression and cancers has been a focus of interest. Our previous studies have shown that Kindlin-2 expression was up-regulated in several types of human cancers, and a strong correlation between Kindlin-2 expression and clinical outcome of breast cancer patients was found. However, the functional role of Kindlin-2 in breast cancer has not been studied. This study was designed to investigate the role of Kindlin-2 in the progression of human breast cancer cells. Methods. Firstly, Kindlin-2 expression at protein level was detected by Western blot in several breast cancer cell lines. Two luminal-like breast cancer cell lines, MCF-7 and T47D, expressed low level of Kindlin-2. Two basal-like breast cancer cell lines, MDA-MB-231 and HS578T, expressed moderate levels of the protein. Then, Kindlin-2 gene was overexpressed by transfected into MCF-7 cells. In comparison, short hairpin RNA (ShRNA)-mediated knockdown of Kindlin-2 was performed in HS578T cells. Vector controls were also done in the same cell lines. Ki67 Li, FCM cell cycle, anchorage-independent colony formation (in vitro tumorigenesis), and in vivo tumorigenesis in NOD/SCID mice were observed. Apoptotic cells were labeled by fluorescent annexin V assay and 86 | Der Pathologe · Supplement 1 · 2012 quantified by FACS. Array CGH analysis and spectral karyotyping were performed to detect the genomic instability of these cells. Results. The growth rate of Kindlin-2-transfected MCF-7 cells was much quicker than that of the controls. The proportion of G2-M phase cells, clone formation and tumorigenicity were significantly higher than these of the controls. The change of Kindlin-2-ShRNA transfected cells was just the reverse. Moreover, Up-regulation of Kindlin-2 can also reduce the rate of apoptosis induced by the chemotherapy drugs, and these cells showed much more genomic instability compared with the controls. Conclusions. These findings suggested that up-regulation of Kindlin-2 promotes the progression of human breast cancer cells by increasing their proliferation, drug resistance, genomic instability, and tumorigenesis. SG-142 ECRG4 is frequently downregulated by CpG island hypermethylation in human breast cancer W . Zhang1 1Zhejiang University, Institute of Pathology, Hangzhou, China Aims. Esophageal cancer related gene4 (ECRG4) is a recently reported candidate tumor suppressor gene frequently hypermethylated in several human tumor types, including esophageal squamous cell carcinoma, colorectal carcinoma, glioma and prostatic carcinoma. This study is to investigate if ECRG4 is transcriptionally silenced by promoter CpG island methylation in breast cancer. Methods. We analyzed several breast cell lines and 12 pairs of fresh samples from breast cancer patients for ECRG4 promoter CpG island methylation by COBRA and bisulfite sequencing. ECRG4 mRNA and protein expression analysis was carried out by semi-quantitative RT-PCR, realtime PCR, Western Blot and immunohistochemistry. Results. We found that all of three immortalized normal breast cell lines and three normal breast tissues expressed ECRG4 proteins, whereas ECRG4 expression were reduced or absent in most breast cancer cell lines and primary breast cancer samples. We also identified that ECRG4 promoter was frequently methylated in breast cancer samples. An inverse correlation between mRNA expression and methylation status of the ECRG4 promoter CpG island was observed in primary breast cancer samples. Conclusions. The expression of ECRG4 is frequently decreased due to promoter CpG island hypermethylation in breast cancer. SG-143 Novel biomarkers in breast carcinoma: DKK3, ITIH5, SFRP-1 V . Kloten1 , B . Becker1 , M .G . Schrauder 2 , P .A . Fasching 2 , A . Hartmann3 , J . Veeck1 , R . Knüchel1 , E . Dahl1 1University Hospital of the RWTH Aachen, Institute of Pathology, Aachen, 2University Hospital Erlangen, University Breast Center, Erlangen, 3University Hospital Erlangen, Erlangen Aims. For early detection of breast cancer the development of robust blood-based biomarkers that accurately reflect the host tumor is mandatory and thus a growing field of research. The most common alterations in human cancers including breast cancer are changes in the status of DNA methylation, which are therefore quickly emerging as a new pool of potential biomarkers. Thus, we investigated the feasibility of detecting aberrant tumor suppressor gene methylation in cancer cell-derived free circulating DNA in the bloodstream of patients. Methods. Using qualitative MSP, we examined the methylation status of six biologically significant putative tumor suppressor genes, i.e. ITIH5, DKK3, WIF1, SFRP1, SFRP2 and SFRP5 in DNA extracted from serum. Clinical performance was determined in a large training study on 150 serum samples (120 breast cancers, 30 healthy controls). 20 benign di-
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Inhalt Der Pathologe · Supplement
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Inhalt Der Pathologe · Supplement
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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
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 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 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
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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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