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

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Keynote Lecture VO-014 Genetic determinants for cancer progression and individual therapy selection A . Ullrich 1 1Department of Molecular Biology, Max Planck Institute of Biochemistry, Martinsried For the past years we have investigated various aspects of signaling systems in tumor cells in order to identify critical switch points in the patho-physiological process that results in malignancy. These efforts aim at the selective blockade of abnormal, disease-promoting signaling mechanisms by monoclonal antibodies, or small molecule kinase inhibitors. This strategic approach began with the cloning of the EGF receptor cDNA and the related receptor HER-2/neu and translated the animal oncogene concept into target-directed personalized therapy of human cancer. This work yielded the first specific oncogene target-based, FDAapproved (1998) therapeutic agent, “Herceptin”, for the treatment of metastatic breast cancer. Earlier and subsequent “target-driven drug development” efforts that employed various genomic analysis strategies led to the cancer therapies that are based on EGFR, HER3, FGFR4, Axl/Ufo and Flk-1/VEGFR2 as critical signaling elements in tumor progression. The latter served, in cooperation with SUGEN Inc./Pharmacia/Pfizer, as basis for the development of SU11248. The drug discovery process that led to SU11248 represents a prototypical example for the adaptation of cancer therapeutics from highly specific to multi-targeted drugs. While all novel cancer therapies target genetic alterations in tumor tissues innovative strategies are aimed at investigating the contribution of germ line determinants of the patient to disease progression and therapy response. One example is the common polymorphism at codon position 388 in the human FGFR4 gene of which the Arg388 allele represents a target for the development of individual genotype-dependent cancer therapy development. Current findings and their consequences for patient-specific cancer therapy will be discussed. PSI Grünewald Neu: EXAKT Pathosäge, Arbeitssicherheit, Diamant-Trennband, Edelstahlausführung • Abstrichinstrumente • Objektträger-Aufbewahrung • Färbeautomaten • Laborabzugsgeräte • Sonderlösungen/-entwicklungen PSI Grünewald Gottlieb-Daimler-Straße 1, 69514 Laudenbach Tel.: 06201/71343, Fax: 06201/45542 psi-gruenewald@t-online.de, www.psi-gruenewald.de Translationale Forschung und Diagnostik – Lunge, Sarkome, GIST VO-015 Translational lung cancer research S . Perner1 1University Hospital of Bonn, Institute of Pathology, Bonn Lung cancer is the most common malignant disease leading to death worldwide. Histologically, it is broadly subcategorized into small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC), with the latter mainly consisting of the three major entities – adenocarcinoma, squamous cell carcinomas and large cell carcinomas. In the recent past, surgical resection and chemotherapy were the only therapeutic options available. However, genetic profiling of various lung cancer entities have revealed major genetic differences within distinct histological tumor entities, enabling specific diagnosis, individual prognosis and rational treatment for the disease. Mutation of the Epidermal Growth Factor Receptor (EGFR) in lung cancer of non-smoking patients was the first major discovery leading to novel therapeutic strategies, which included treatment with tyrosin kinase inhibitors (TKI) gefitinib and erlotinib. EGFR mutated cases are more sensitive to TKI treatment, whereas cases harboring KRAS mutations are associated with a resistance to TKI. Moreover, the occurrence of KRAS and EFGR mutations are mutually exclusive and are correlated with poor prognosis. In an effort to further subclassify lung cancer at the molecular level, large lung cancer cohorts were characterized using high-throughput technologies. The lineage survival oncogene TTF1 is found to be the most common amplification occurring in pulmonary adenocarcinomas. In squamous cell lung cancer, SOX2 was identified as the most frequently amplified lineage survival oncogene. Amplification of either gene proved to be associated with better overall survival rates. In 2010, Weiss et al. described Fibroblast Growth Factor Receptor 1 (FGFR1) amplification in 20% of squamous cell lung cancer. FGFR1 amplified tumors were shown to be sensitive to FGFR1 small molecule inhibitors in cell lines and murine xenograft models. This finding paved the way to the first rational therapy in a significant subset of molecularly defined squamous cell lung cancers. Moreover, our discovery of FGFR1 amplification in squamous cell cancers of the head and neck area might broaden the therapeutic spectrum of the FGFR1 inhibitors. These findings, among others, can only estimate the genetic complexity of lung tumors. Large-scale molecular profiling has the potential to identify novel diagnostic, prognostic and predictive markers as well as therapeutic targets.
Abstracts VO-017 Translational research and diagnostics – GIST E . Wardelmann 1 1 University of Cologne, Institute of Pathology, Köln Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors in the digestive tract. In up to 90% of cases, they are characterized by activating mutations in the KIT or the PDGFRA gene. GIST turn out to be a paradigm for successful targeted treatment with tyrosine kinase inhibitors (TKI). Since the approval of the TKI imatinib in 2002 the survival of patients with metastatic GIST has been tripled. The next logical step was the concept to use imatinib in an adjuvant approach which recently showed to increase the overall survival significantly. In both settings, the mutational status has high predictive implications. In detail, GIST with KIT exon 11 mutations show the best response rates with partial remission rates of up to 80%. In KIT exon 9 mutations, a doubled daily dose of 800 mg imatinib is now the standard. The PDGFRA exon 18 mutation D842V has been shown to lead to a primary resistance. Conclusively, the treatment strategy in GIST is driven by their molecular characterisation. Further research has increased the knowledge about resistance mechanisms in solid tumors against TKI. The number of patients with secondary resistance due to acquired KIT mutations is increasing with treatment duration. Strategies to address this situation are the introduction of novel pathway inhibitors targeting different levels of signal transduction pathways such as the mTOR/Akt pathway, the RAS/RAF pathway, histone deacetylation, and others. Among the GIST without mutations in the common hot spot regions of KIT and PDGFRA, so-called wild type GIST, further genomic subgroups have been identified. One such subgroup carries inactivating germline mutations in the genes encoding succinate dehydrogenase B, C, or D. They are associated with the occurrence of paragangliomas, the so-called Carney-Stratakis syndrome. Most frequently, GIST are located in the stomach and show an epithelioid phenotype and a multinodular growth pattern. They preferentially occur in young females and often show lymph node metastases. In Carney’s triad additional pulmonary chondromas are observed. Another small subgroup of sporadic GIST present with BRAF mutations as an alternative genomic event. Finally, very rare kindreds with germline mutations in either KIT or PDGFRA have been described. In summary, the molecular characterisation of GIST has revolutionized their treatment because of increasing knowledge about the high relevance of predictive molecular typing in solid tumors. Translationale Forschung und Diagnostik – Niere, abl. Harnwege, Prostata VO-018 Biomarker for diagnosis, prognosis and prediction in renal cancer H . Moch1 1University Zurich, Institute for Pathology, Zürich, Switzerland Biomarkers are frequently used in aiding diagnosis, and to predict prognosis or response to therapy in neoplasms. In renal cancer, immunohistochemistry is commonly used in the routine for the classification of renal tumors. Conventional karyotyping, fluorescence in situ hybridization and molecular cytogenetics are less commonly used. Expression profiling, and mutational analysis are currently performed to identify specific molecular pathways in renal cancer, mainly for research purposes. In this presentation, we document results of a Working Group Meeting conducted by the International Society of Urological Pathology (ISUP) in 10 | Der Pathologe · Supplement 1 · 2012 Vancouver 2012. The Working Group discussed the use of immunohistochemical markers as well as the use of cytogenetics or other molecular technologies in the characterization of renal neoplasms. In this presentation, the results of the Working Group Meeting are summarized. In detail, the value of immunohistochemistry for the differential diagnosis in different diagnostic situations, e.g. in renal tumors with clear or granular cytoplasm, diagnosis of unclassified renal cancer is commented. Further, the view of the Working Group regarding use of predictive or prognostic biomarkers in routine pathology is provided. VO-019 Translational research and diagnostics: urinary tract R . Knüchel-Clarke1 , N .T . Gaisa2 , M . Rose2 , C . Henkel3 , E . Dahl2 1 2 Universitätsklinikum Aachen, Institut für Pathologie, Aachen, University Hospital, RWTH Aachen, Institut für Pathologie, Aachen, 3Ruhr-University Bochum, Medical Proteomics Center, Bochum In urothelial cancer as a frequent tumor entity two main fields of the clinical situation deserve special attention and need support from basic research. 1. Amongst the most frequent non-invasive papillary low grade tumors morphology alone is insufficient to predict recurrence rate or even more importantly progression. 2. Amongst the already muscle invasive tumors which mostly undergo cystectomy, neoadjuvant and adjuvant chemotherapy concepts still have a limited supportive role, and more effective individualized treatment concepts are desirable. Ad 1. While the WHO classification of tumors has integrated data from genetic analysis of tumors to diagnose genetically stable (low grade) and unstable (high grade) tumors, FGFR3 mutations and additional molecular alterations may help to define the non-progressing, i.e. nearly benign tumors within the group of low grade tumors. This could support therapy decision favoring avoidance of intravesical chemotherapy and allowing less follow up. A multiparametric approach will be necessary and becomes increasingly feasible due to e.g. epigenetic or proteomic marker sets. Ideally these marker sets are not only valid for tissue analysis but also sufficiently sensitive to predict benign disease course in cytology specimens. Ad 2. Within the group of genetically instable tumors it seems necessary to define tumors different from mere urothelial differentiation as squamous and glandular as well as variants of urothelial carcinoma as micropapillary or small cell carcinoma in a first step. All these tumor variants are found in other organs as well. Consequently the multicentric collection of cases and the molecular analysis of pathways of growth signalling is an apt approach for target identification. Data should be compared to already established data in other cancers as colon and lung cancer and will allow the inclusion of cases in prospective studies using e.g. small molecule- like tyrosine kinase inhibitors. Own research efforts and recent data from the literature that intend to improve the two clinical settings in urothelial cancer will be presented. With support of a START grant RWTH Aachen (MR, NTG and ED) and a DFG grant GA 1384/2-1 (NTG). VO-020 Translational research and diagnosis of prostate cancer G . Kristiansen1 1Institut für Pathologie der Universitätsklinik Bonn, Bonn Prostate cancer is the most common non-cutaneous malignant tumour in men and is a major research focus of pathologists, urologists and urooncologists alike. Due to PSA-screening and risen patient awareness, the practising pathologist is confronted with a steadily increasing number of prostate biopsies, necessitating ancillary tests in morphologically challenging cases. Next to basal cell markers, additional positive markers
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 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
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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
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SO-027 Ki-67 in mitotic score group
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nificantly associated with advanced
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liver did not correlate with the mu
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AG Paidopathologie II SO-046 Overex
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Results. Histomorphology of the ova
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p42 and p27 have not yet been inves
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SO-068 Recent advances in understan
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SO-075 A novel, dual role of CCN3 i
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Pancreatic Adenocarcinoma SG-137 Se
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sease and 30 colon cancer serum sam
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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
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FR-P-037 MALDI imaging reveals COX7
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in the context of therapy response
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on primary cells of wild-type and c
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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
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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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