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

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p42 and p27 have not yet been investigated in PCa. Therefore, we aimed in this study at investigating the role of ETS-1 in PCa cell lines, and whether the ETS-1 splice variants p42 and p27 are expressed in PCa cell lines. Methods. We first examined the expression of all 27 ETS family members using quantitative RT-PCR in androgen-sensitive and insensitive PCa cell lines. As ETS-1 was found to be highly expressed in the androgeninsensitive PCa cell lines PC3 and DU-145, we investigated the effect of blocking ETS-1 in PC3 cells on genes involved in the metastatic cascade using comprehensive gene expression microarrays, and correlated these findings with PCa tissues. The expression of the ETS-1 splice variants p42 and p27 was assessed using an anti-ETS-1 antibody directed against the DNA-binding domain (DBD), and RT-PCR. Results. Assessment of ETS-1 blockade yielded many genes which are known to be implicated in PCa. Correlating these genes with findings from PCa tissues identified 16 genes that are up or down regulated in healthy compared to tumorous PCa glands. Bioinformatical analysis revealed that 13/16 of these genes have potential ETS-1 binding sites within their promoter regions, and 4 were reported to be regulated by members of the ETS family. Furthermore, our results show for the first time the novel identification of the ETS-1 splice variants p42 and p27 in both the androgen-dependent and the androgen-independent PCa cell lines. Conclusions. Future studies will address the roles of the ETS-1 splice variants in PCa cell lines and tissues. These findings provide in vitro and in vivo evidence for the importance of ETS-1 in development and progression of PCa SO-063 Serum and prostate cancer tissue signatures of ERG rearrangement derived from quantitative analysis of the PTEN conditional knockout mouse proteome N .J . Rupp1 , I . Cima2 , R . Schiess3 , P .J . Schüffler4 , T . Fuchs5 , N . Fankhauser2 , M . Kälin6 , S . Gillessen6 , R . Aebersold3 , W . Krek2 , M .A . Rubin7 , H . Moch1 , P .J . Wild1 1University Hospital Zurich, Institute of Surgical Pathology, Zürich, Switzerland, 2ETH Zurich, Institute of Cell Biology, Zürich, Switzerland, 3ETH Zurich, Institute of Molecular Systems Biology, Zürich, Switzerland, 4ETH Zurich, Department of Computer Science, Zürich, Switzerland, 5California Institute of Technology, Pasadena, CA, United States, 6Cantonal Hospital St . Gallen, Department of Oncology, St . Gallen, Switzerland, 7Weill Cornell Medical College, Department of Pathology and Laboratory Medicine, New York, NY, United States Aims. Applying a systems biology approach to assess serum and tissue signatures of ERG rearrangement in patients with prostate cancer with the goal of determining downstream molecular targets for gene fusion cancers. Methods. Prostate tissue from a conditional PTEN knockout mouse model of prostate cancer was investigated, using selective enrichment of N-glycopeptides and mass spectrometry-based label-free quantification. Mouse tissue signatures were validated in sera and tissue of mice (n=12) and humans (n=105) by selected reaction monitoring (SRM), ELISA, and immunohistochemistry. ERG rearrangement status was assessed using fluorescence in situ hybridization (FISH) on two independent tissue microarray based prostatectomy cohorts (n=41, n=348). A Random forest model was trained and validated to identify serum and tissue signatures of ERG rearrangement. Results. A comprehensive PTEN dependent protein catalogue representing over 700 glycoproteins was established. TMPRSS2-ERG gene fusions occurred in 41% (17/41) of analyzable prostate cancers of the training cohort. ERG dependent serum signatures could be found. Predicted serum signatures were systematically tested on two prostate cancer tissue microarrays (training and test cohort) using immunohistochemistry for 15 candidate proteins and members of the PI3K/AKT/mTOR pathway. Conclusions. This is the first study to demonstrate a proteomic signature of ERG rearrangement prostate cancer. Given the challenges of directly targeting ETS transcription factors, this study has potential clinical im- plications providing important insights into future targetable downstream pathways. SO-064 Landscape of chromosome number changes during prostate cancer progression J . Stomper1 , M . Braun1 , W . Vogel1 , D . Böhm1 , V . Scheble2 , F . Fend3 , S . Perner1 1 2 University Hospital of Bonn, Institute of Pathology, Bonn, University Hospital of Tübingen, Division of Oncology, Tübingen, 3University Hospital of Tübingen, Institute of Pathology, Tübingen Aims. Genetic instability resulting in both aneuploidy and polyploidy is discussed to be involved in prostate cancer (PCa) development and progression. However, a complete survey of numerical chromosomal changes in PCa is lacking so far. The aim of this study was to comprehensively characterize the ploidy level in PCa with regard to disease progression via fluorescence in situ hybridization (FISH). Since aneuploidy and aggressive disease are often associated with increased tumor cell proliferation, we also assessed the expression of two common mitosis markers within the same PCa cohort. Methods. We studied a cohort comprising 186 localized PCa, 75 PCa with 125 corresponding lymph node metastases, and 42 hormone-refractory distant metastases. Using dual-color FISH, we assessed the cohort for losses and gains of all 24 chromosomes. Conducting immunohistochemistry studies with the markers pHH3 and Ki67, we quantified the proliferation rate within the same cohort. Results. We observed a sharp and significant increase in aneuploidy with advancing tumor stage (p
Abstracts SO-065 Mutation analysis of squamous bladder tumours N .T . Gaisa 1 , J . Korb 1 , N . Reimer 1 , S . Denzinger 2 , S . Koufou 2 , E . Eltze 3 , M . Toma 4 , S . Siegert 5 , A . Hartmann 6 , R . Stöhr 6 , R . Knüchel 1 1 RWTH Aachen University, Institute of Pathology, Aachen, 2 University Hospital Regensburg, Department of Urology, Regensburg, 3 Institute of Pathology Saarbrücken-Rastpfuhl, Saarbrücken, 4 University Hospital Dresden, Institute of Pathology, Dresden, 5 LMU Munich, Institute of Pathology, München, 6 University Hospital Erlangen, Institute of Pathology, Erlangen Aims. The identity and impact of genetic changes in non-Schistosoma associated squamous carcinoma of the bladder and urothelial carcinoma with squamous differentiation are still unknown. Therefore, in this study squamous tumours have been analyzed for frequent somatic mutations in urothelial cancer. Methods. Pure squamous carcinoma (n=34) and mixed urothelial cancers with additional squamous differentiation (n=42) as well as their precursor lesions have been screened for mutations in TP53, FGFR3 and PIK3CA. Sanger Sequencing was performed for TP53; FGFR3 and PIK3CA were analyzed by SnapShot-method. Results. 47% of pure squamous carcinoma (16/34) and 62% of urothelial cancer with squamous differentiation (26/42) showed TP53 mutations. The most frequent mutation was p.R175H (5 times, 3 in pure squamous carcinoma, 2 in mixed carcinoma). FGFR3 mutations (exclusively S249C) were detected in 9% (3/34) and 12% (5/42) respectively, PIK3CA mutations (E542K and E545K) in 18% (6/34) and 17% (7/42). Both FGFR3 and PIK3CA mutations were found in 2 patients (pure squamous carcinoma) only. TP53 and FGFR3/PIK3CA mutations were not mutually exclusive, and TP53 mutations associated with either FGFR3 or PIK3CA mutations were found in 9 cases (n=4 pure squamous carcinoma, n=5 mixed carcinoma). FGFR3 mutations were not related to any particular morphological phenotype. Conclusions. TP53 mutations occurred with slightly higher frequency in squamous parts of mixed carcinoma, but the overall incidence of TP53 mutations was similar to reports of pure urothelial carcinoma in the literature. TP53 mutations may play a critical role in the development of squamous bladder tumours, whereas FGFR3 and PIK3CA mutations seem to be less relevant. SO-066 The impact of bladder cancer histology on overall survival of patients treated by cystectomy and adjuvant cisplatin-based chemotherapy B . Keck1 , R . Stöhr2 , S . Wach1 , H . Taubert1 , F . Kunath1 , S . Bertz2 , J . Lehmann3 , M . Stöckle4 , B . Wullich1 , A . Hartmann2 1 2 University of Erlangen, Department of Urology, Erlangen, University Erlangen, Department of Pathology, Erlangen, 3Urology Practice Prüner Gang, Kiel, 4Saarland University, Department of Urology Aims. To evaluate the impact of conventional urothelial (UC), plasmacytoid (PUC) and micropappilary (MPC) histology on survival of bladder cancer patients treated by cystectomy and adjuvant cisplatin-based chemotherapy within the prospective and randomized trial AUO-AB05/95. Methods. Tumor samples of 221 patients with a majority treated within the randomized AUO-AB05/95 trial by radical cystectomy and adjuvant cisplatin-based chemotherapy were reviewed for identifying histologic subtypes of locally advanced bladder cancer. 191 UC, 20 PUC and 10 MPC of the bladder were identified. For the definition of PUC and MPC, at least 50% of the tumor had the specific histologic pattern. Kaplan Meier analysis and multivariate Cox’s proportional hazards regression analysis were performed to compare overall survival (OS) of UC, MPC and PUC. Of these 221 patients, 50 patients were treated with gemcitabine/cisplatin, 83 patients with M-VEC and 88 patients with cm. Results. Median OS of PUC was 29.9months and significantly worse compared to patients suffering from UC (62.8 months) or MPC (64.2 months; 80 | Der Pathologe · Supplement 1 · 2012 p=0.04). Multivariate Cox’s proportional hazards regression analysis adjusted to chemotherapy showed a hazard ratio of 1.9 (p=0.034) for UC (n=191) and 2.7 (p=0.083) for PUC (n=20) in contrast to patients suffering from MPC (n=10). Conclusions. Bladder cancer histology gives important information on the prognosis of patients suffering from locally advanced bladder cancer. As OS of UC, PUC and MPC differs in patients treated by radical cystectomy and adjuvant cisplatin-based chemotherapy further prospective studies comparing histologic variants of bladder cancer are necessary in order to tailor therapeutic strategies in the future. SO-067 Prognostic role of androgen receptor in bladder cancer R . Wirtz1 , S . Bertz2 , B . Keck3 , S . Claas2 , L . Dyrskjøt4 , T . Orntoft5 , B . Wullich3 , R . Hake6 , S . Eidt6 , A . Hartmann1 1 2 University Cancer Center Erlangen, Institute of Pathology, Erlangen, University Cancer Center Erlangen, Institute of Pathology, 3University Cancer Center Erlangen, Urology University Clinic, 4Aarhus University Hospital, Denmark, 5Aarhus University Hospital, Molecular Medicine, Denmark, 6Institute of Pathology at the St-Elisabeth-Hospital Cologne Aims. Hormone receptors are the prototype predictive marker in breast and prostate cancer. Hormone receptor positive cancers have a better prognosis, increased tropism to metastasize into the bones and respond to endocrine treatment options. The prognostic value of hormone receptor in urothelial carcinoma of the bladder (UCB) is less established. This may in part result from technical limitations of immunhistochemical detection methods. Interestingly, female gender has recently been identified as strong adverse factor in advanced UCB (May et al. 2011). By analyzing whole genome expression data from non-muscle invasive bladder cancer patients, we have evaluated the potential of top candidate genes (ESR1, PGR, AR, CYP19, HER2, RACGAP1) commonly used to stratify breast cancer patients to predict bladder cancer progression. In view of the gender specific effects, we have focused on the prognostic role of androgen receptor expression on tumor invasion, disease progression and survival. Methods. Affymetrix microarray data from 41 non-metastatic bladder cancer patients undergoing curative surgery were analyzed. Prognostic value of androgen receptor mRNA expression was analyzed by unsupervised Cluster analysis, partitioning tests, Mann Whitney tests and Kaplan Meier estimates of cancer specific survival. Results. Cluster analysis in the microarray date of the superficial UCB cohort identified a hormone receptor positive subtype and a proliferation dominated subtype of equal size. Androgen receptor expression was negatively associated with cancer specific death (r=−0.42; p=0.005), while proliferation correlated with increased risk of cancer specific death (r=0.46; p=0.003). In addition, low androgen receptor expression was associated with higher tumor stage (pTa vs pT1-4; p=0.017). In Kaplan Meier analysis, the cancer specific survival was significantly better in tumors exhibiting high androgen receptor levels (80% vs. 20%; p
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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,
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 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 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 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
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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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