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

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or BRAF mutation, c-MYC and SIRT1 expression was not found increased. In addition, within the group of serrated lesions with wild type KRAS and BRAF, a subgroup was characterized by elevated c-MYC and SIRT1 expression. In these lesions with mostly high grade intraepithelial neoplasia and carcinomas, nuclear localization of β-catenin suggested that activation the wnt signalling pathway may mediate the induction of c-MYC at the transcriptional level. Conclusions. In summary, we established a link of oncogenic K-Ras and B-Raf as well as wnt signalling to activation of the c-MYC oncogene and SIRT1 in the serrated route to colorectal cancer. The elevated expression levels observed within higher grades of malignancy point to a crucial function of c-MYC and SIRT1 in the malignant transformation. AG Pneumopathologie I DO-025 HOPE-technique improves diagnostics of Bronchoalveolar Lavage (BAL) E . Vollmer 1 , S . Marwitz1 , M . Abdullah1 , C . Vock1 , J .S . Fine2 , S . Visvanathan2 , K . Gaede1 , H .-P . Hauber1 , P . Zabel1 , T . Goldmann1 1 2 Research Center Borstel, Borstel, Roche, Inflammation Discovery, United States Aims. Besides its application in pulmonary routine diagnostics BAL is a useful tool for scientific investigations. Because of its limitations in long term storage we explored in this study the utility of a novel fixative (HOPE, Hepes glutamic acid buffer mediated Organic solvent Protection Effect) for retrospective and standardized cell analysis also in regard of immunological and molecular techniques. This study has been performed in accordance with the 1964 Declaration of Helsinki and its later amendments. Methods. BAL samples, obtained by flexible bronchoscopy from patients with different diseases, were diluted to a standard cell number of one million cells and incubated in HOPE-fixative as well as in neutral buffered 4% formalin with a subsequent paraffin-bloc-embedding. In addition, for addressing RNA preservation, fresh frozen samples were included. For enhanced/expanded high-throughput analyses of multiple BAL samples tissue microarrays of paraffin embedded HOPE-BAL were also produced. Results. We have shown that HOPE-BAL cells have an excellent morphology; besides that this technique allows archiving of BAL cells. By preservation of proteins and nucleic acids it allows the application of immunocytochemistry as well as a plethora of molecular techniques like in situ hybridization, quantitative PCR, transcription microarray analysis, 2-D-Gel-Electrophoresis etc. We showed by targeting some exemplary molecules the power of screening and validating HOPE-BAL for new biomarkers. Conclusions. The HOPE-BAL-technique allows long term storage of BAL cells and is a unique and novel tool for various molecular based applications in pulmonary medicine. It combines easy handling in the form of paraffin blocks with almost no limitations in readout techniques thus being a step forward into enhanced molecular diagnostics and biobanking. DO-026 Tissue sparing application of the newly proposed IASLC/ATS/ ERS classification of non-small cell lung cancer shows practical diagnostic and prognostic impact W . Sterlacci1 , S . Savic2 , T . Schmid3 , M . Fiegl4 , A . Tzankov 2 1 2 Academic Teaching Hospital Feldkirch, Feldkirch, Austria, University Hospital Basel, Switzerland, 3Medical University Innsbruck, Center of Operative Medicine, Austria, 4Medical University Innsbruck, Department of Internal Medicine, Austria Aims. The histologic subtype of non-small cell lung cancer (NSCLC) determines treatment strategies and the need for genetic analyses. Since most NSCLC are diagnosed on small biopsies or cytology specimens, an accurate but also tissue sparing approach is necessary. To date, consensus for a general diagnostic algorithm is lacking. Methods. To test the diagnostic and clinical relevance of the recently published multidisciplinary guidelines by the International Association for the Study of Lung Cancer, American Thoracic Society and European Respiratory Society, we examined 371 surgically resected NSCLC brought into tissue microarray format as a surrogate for small biopsies. Adenocarcinomas (ACA) were graded according to architecture considering lepidic as well, acinary and papillary as moderately and micropapillary and solid as poorly differentiated. Results. The antibody panel TTF-1, p63, CK5/6 and CK7 proved diagnostic for most cases. The positive predictive value (PPV) of p63 and CK5/6 for squamous cell carcinoma (SCC), and of CK7 and TTF1 for ACA was 88.9%, 84.9%, 88.4% and 97.7%, respectively. The negative predictive value (NPV) of p63 and CK5/6 for SCC, and of CK7 and TTF1 for ACA was 99.5%, 99.5%, 93.6% and 76.9%, respectively. Faint/focal staining for CK7 is negligible for classificatory purposes and focal expression of TTF-1 with variable staining intensity is a feature compatible with SCC (approximately 3% of cases). Overall survival in months for ACA according to architecture-based tumor grade was 72.5 for well, 71.0 for moderate and 35.7 for poor differentiation (p=0.039). Conclusions. We propose double stains combining an above mentioned nuclear and membranous marker, which is highly diagnostic for NSCLC on small biopsies while conserving tumor tissue for subsequent analyses. No recommendations using less than 2 sections exist, however a panel consisting of TTF-1 in combination with CK5/6 may be feasible, since TTF-1 appears to be the most specific discriminating marker between ACA and SCC (best PPV for ACA) and the only unequivocally evaluable staining combination is with cytoplasmic staining for CK5/6, which also achieved the best NPV for ACA. When grading ACA, the histologic tumor architecture should be the determining factor. This approach primarily has prognostic implications but will also result in easier comparisons of future studies. DO-027 Multi-immunassay with concurrent staining of 6 antibodies allows tissue-sparing diagnosis on small tissue samples on nonsmall cell lung carcinomas with high diagnostic accuracy G . Kayser1 , A . Csanadi 1 , C . Otto1 , S . Dango2 , B . Passlick2 , M . Werner1 1 2 Institute of Pathology, University Hospital Freiburg, Freiburg, Department of Thoracic Surgery, University Hospital Freiburg, Freiburg Aims. Today the histological differentiation of non-small cell lung carcinomas NSCLC into adenocarcinomas (LAC), squamous cell carcinomas (SCC), and large cell neuroendocrine carcinomas (LCNEC) is not only of prognostic relevance but far more of predictive value for different therapeutic regimes. As these decisions are of utmost relevance in advanced cancer stages, pathologists are asked to perform a highly accurate diagnosis on small tissue samples. We here investigated the possibility of simultaneous staining of widely agreed upon markers for the histological classification of NSCLC. Der Pathologe · Supplement 1 · 2012 | 21
Abstracts Methods. Of 261 NSCLC patients tissue multi arrays (TMA) with a core diameter of 2 mm were composed which served as a simulation model for endobronchial biopsies. The TMAs were stained with TTF1 (8G7G3/1) and Vimentin (VIM3B4) visualized by amino-ethylcarbazol first. Second staining was performed with p63 (4A4) and a neuroendocrine (NE) cocktail (CD56 (NCL-L-CD56-1B6), synaptophysin (SPII), chromogranin (DAK-A3)) visualized by diaminobenzidine. For histological classification hematoxilin-eosin (HE) stained TMA-slides were evaluated. Independently from HE-classification immunohistochemical (IHC) classification was performed by a stepwise decision tree: 1) morphologically clear adenoid or squamous growth patterns: LAC or SCC; 2) TTF1 positive: LAC; 3) TTF1 negative and p63 positive: SCC; 4) TTF1 and p63 negative: large cell carcinoma; 5) TTF1 negative, p63 negative, NE positive: LCNEC. Statistical analyses included kappa-values and Kaplan Meier survival curves. Results. Evaluation of specific staining of the different antibodies was easy to perform and compared to a set of carcinomas which were stained with the multi-IHC protocol and each antibody separate did not show any different staining patterns. Analyzing the inter-core variability, IHC classification was superior to HE-diagnosis. Furthermore, a better separation of the Kaplan-Meier survival curves could be achieved by IHC classification as compared to HE classification alone. Conclusions. Multi-immune assays for classification of NSCLC are feasible and deliver more accurate results than HE-diagnosis alone. IHC classification shows higher intra-tumor homogeneity. As different entities are most probable to show different biological behavior IHC classification delivers the best separation of survival curves and should thus be applied to all lung cancer specimens for accurate pathological classification on small biopsies. DO-028 The novel IASLC/ATS/ERS classification is a stage-independent predictor of survival and correlates with the response to adjuvant therapies A . Warth1 , T . Muley2 , M . Meister3 , A . Stenzinger1 , J . Cortis1 , M . Thomas4 , P . Schirmacher1 , P .A . Schnabel1 , J . Budczies5 , H . Hoffmann6 , W . Weichert1 1 2 University Hospital Heidelberg, Institute for Pathology, Heidelberg, Thoraxklinik Heidelberg, Translational Research Unit, 3Heidelberg University Hospital, Translational Research Unit, 4Thoraxklinik Heidelberg, Oncology, 5 6 Charité University Hospital Berlin, Institute for Pathology, Thoraxklinik Heidelberg, Thoracic Surgery Aims. Our aim was to analyze and to validate the prognostic impact of the novel IASLC/ATS/ERS proposal for an architectural classification of invasive pulmonary adenocarcinomas (ADC) across all tumor stages. Methods. The architectural pattern of a large cohort of 500 resected ADC (stages I–IV) was retrospectively analyzed in 5% increments and classified according to their predominant architecture (lepidic, acinar, solid, papillary, micropapillary), as proposed by the IASLC/ATS/ERS. Subsequently, histomorphological data were correlated with clinical data, adjuvant therapy and patient outcome. Results. Overall survival differed significantly between lepidic (78.5 months), acinar (67.3 months), solid (58.1 months), papillary (48.9 months), and micropapillary (44.9 months) predominant ADC (p=0.007). When patterns were lumped into groups this resulted in even more pronounced differences in survival (pattern group 1: 78.5 months, group 2: 67.3 months, group 3: 57.2 months, p=0.001). Comparable differences were observed for overall, disease specific and disease free survival. Pattern and pattern groups were stage- and therapy-independent prognosticators for all three survival parameters. Survival differences according to patterns were influenced by adjuvant radiochemotherapy, especially solid predominant tumors had an improved prognosis under adjuvant radiotherapy. The predominant pattern was tightly linked to the risk of developing nodal metastases (p
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 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 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
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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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