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

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SA-P-085 Expression of the eukaryotic translation initiation factor 3a in urinary bladder cancer R . Spilka 1 , A .K . Mehta 2 , J . Haybaeck 2 , P . Obrist 1 1 Pathologylab Dr . Obrist & Dr . Brunhuber OG, Zams, Austria, 2 Institute of Pathology, Medical University of Graz, Austria Aims. Urinary bladder cancer (UBC) is a frequent and aggressive urinary tract cancer, of transitional cell type, with high mortality rates. One obstacle in defining novel treatment approaches is that the cancer’s aetiology and genetics are not yet completely understood. eIF3a, the largest subunit of eukaryotic initiation complex eIF3, is up-regulated in many cancers including breast, cervix, colon, esophagus, lung and stomach and its suppression leads to inhibition of tumour cell proliferation in vitro. We are therefore aiming at evaluating the translation initiation factor eIF3a in UBC to gain insight in the pathogenesis of these tumors and to further determine the role of eIF3a in cancer development and progression. Methods. eIF3a expression was determined by immunohistochemistry on paraffin embedded tissues from 178 UBC patients. Protein expression levels of eIF3a were analysed in five UBC cell lines by western blotting. Furthermore by manipulating eIF3a levels in tumor cell lines, HT1197 and RT4-31, we want to explore whether eIF3a expression levels can directly influence global as well as specific translation and proliferation. We are therefore generating an inducible shRNA mediated eIF3a-knockdown construct for lentiviral transfection. Results. eIF3a is upregulated in UBC when compared to normal tissues, similar to the cancer entities where eIF3a was described to be overexpressed before. We have successfully tested two lentiviral shRNA constructs for the inducible knockdown of eIF3a. The knockdown construct generated proves efficient in all tested cell lines and first results show an association of eIF3a knockdown with growth retardation of tumor cells. Conclusions. Overexpression of eIF3a seems to be tumor-associated over a wide range of tumor entities, with a potential as prognostic marker. The knockdown of eIF3a leads to reduced proliferation rates, indicative of subcellular changes arising probably not exclusively from altered translational profiles. SA-P-086 A case of clear cell renal carcinoma arising in a renal angiomyolipoma A . Dellmann1 , A . Vandromme2 , P . Hammerer2 , K . Donhuijsen1 1Academical Hospital Braunschweig, Department of Pathology, Braunschweig, 2Academical Hospital Braunschweig, Department of Urology, Braunschweig Aims. Renal angiomyolipoma (AML) is a mesenchymal tumor of the kidney that usually shows a benign course. MRI usually enables reliable detection of fat, which is typical for angiomyolipoma, and allows the differentiation to a renal cell carcinoma. We present a rare case of a renal cell carcinoma appearing in AML, thus showing that clear cut diagnosis of AML in MRT in not always possible. Methods. We report about a case of a renal cell carcinoma appearing in AML in a 77-year-old male. Pretherapeutic radiologic imaging of the tumour was fitting for AML. Histological examination including immunohistochemistry was performed. Results. In this case of an AML appearing in the right kidney the pretherapeutic imaging was typical. Histologic examination showed a combined tumour with features of an AML and of renal cell carcinoma within. Immunohistochemical studies showed typical results for AML on the one hand and for RCC on the other. Chromosomal aberrations will be examined by FISH. Conclusions. Angiomyolipoma is a combined mesenchymal tumour of the kidney with a usually benign course. Tumour can be associated with tuberous sclerosis. Although MRI usually allows the differential diagnosis to a renal cell carcinoma, in our case a RCC was found within the AML. The possibility of RCC appearing in AML has to be kept in mind. SA-P-087 Proteomic analysis of renal cell carcinoma and adjacent normal fresh, snap-frozen tissue by MALDI Imaging mass spectrometry B . Häupl1 , C . Recktenwald1 , D . Berger2 , H .-J . Holzhausen2 , F . Bartel2 , B . Seliger1 1University of Halle-Wittenberg, Institute of Medical Immunology, Halle/ Saale, 2University of Halle-Wittenberg, Institute of Pathology, Halle/Saale Aims. Renal cell carcinoma (RCC) is the most common renal malignancy among the tumors that are highly resistant to systemic therapy. However, specific biomarkers for this tumor entity are not well defined. In order to understand the biology of the tumor and to detect features which allow the distinction between tumor and adjacent renal tissue and thus may serve as specific diagnostic biomarkers, in situ-proteome profiling of matched tumor and normal kidney tissue sections was carried out. Therefore, respective biopsy samples were dissected and analyzed via MALDI Imaging mass spectrometry (MALDI-IMS). Methods. Cryosections (thickness 8 μm) of 28 fresh frozen tumor samples and the respective adjacent kidney tissue were mounted onto conductive glass slides and coated with sinapinic acid using an automated spraying device (Bruker ImagePrepTM) after the removal of salts and lipids by several washing steps in graded ethanol solutions. Subsequently the samples were subjected to mass spectrometric measurement with a MALDI-TOF MS device (Bruker ultrafleXtremeTM) in linear positive detection mode operating at the following parameters: i) lateral resolution of 100 μm, ii) mass range between 2 to 20 kDa and iii) 500 laser shots per measurement position. MS data was further processed using a software application specialized for MALDI-IMS analysis (Bruker flexImaging) and the Bruker Clinprotools software package. Results. Data analysis led to the generation of specific average spectra for tumor and normal renal tissue. Although the spectra show a quite similar peak pattern, tumor and normal specific features could be detected. The significance of these features, which subsequently will be subjected to mass spectrometric identification, is currently analyzed by different algorithms such as Support Vector Machine, Genetic Algorithm or Quick Classifier. Conclusions. Tissue proteome profiling via MALDI-IMS is able to detect differentially expressed features and thus allows the identification of biomarkers for improved diagnosis that may be further used as targets for immunotherapy of RCC. SA-P-088 Is the mucinous tubular and spindle cell carcinoma of the kidney a distinct entity or not? I . Kollecker1 , A . Dellmann1 , P . Hammerer2 , K . Donhuijsen1 1Academical Hospital Braunschweig, Department of Pathology, Braunschweig, 2Academical Hospital Braunschweig, Department of Urology, Braunschweig Aims. Mucinous tubular and spindle cell carcinoma (MTSCC) is a rare, low grade renal epithelial neoplasm included into the WHO since 2004 as a distinct entity. However, with rising numbers of such cases the histologic pattern is more and more expanding. The discrimination from papillary renal cell carcinoma (PRCC) on the one hand and the undifferentiated renal cell carcinoma on the other can be problematic. The question arises whether it is really a distinct tumor entity or an new hotchpotch of renal cell carcinoma. Methods. We report about a little series of cases with tubular and mucinous pattern suspect for the diagnosis of MTSCC. The cases were selected from urologic specimen with 108 non-clear cell carcinoma out of the last five years. The tumors were analysed on paraffin slides stained Der Pathologe · Supplement 1 · 2012 | 165
Abstracts by H&E, Pas-Alcian and immunohistochemical staining by CK7, CK 19, EMA, AMACR, Vimentin, NSE, Chromogranin, Synaptophysen, CD 10, CD 15, CD 57 and Ki-67. A FISH-analysis was done for chromosom 7 and 17. Results. Classic cases of MTSCC mainly show a relative homogeneous tubular architecture with low grade morphology and typical mucinous stroma. The latter react pale for Pas and contains in Acian-blue-reaction acid mucopolysaccids. In most cases more or less areas of papillary, plexiforme or glomeruloid growth pattern exists. In parts with very close packed tubuli the cells become a spindle shape character because of compression of the tubulus but with predominant low grade atypia. Immunohistochemistry react positive for CK 7, Ck 19, EMA, AMACR and Vimentin. Neuroendocrine markers show different pattern. CD 10 reacts negative. FISH-analysis brought different results for PRCC and MTSCC. Conclusions. The main part of the MTSCC represents the described tubular architecture with low grade atypia and typical mucinous extracellular stroma component in variable dimension. Despite the classic pattern different extent of other differentiation pattern like papillary, spindle shaped, plexiforme or glomeruloid occur in the cases. Only in exceptions tubular growth pattern was displaced by last named differentiations. Especially papillary growth pattern make it difficult to distinguish MTSCC from other renal cell carcinomas especially PRCC. The demarcation to the other types is important because of prognostic differences. Immunohistochemistry could help with CD 10 negativity but this reaction is however non-specific. Against this background molecularpathologic methods are due to help, but also with limitations. SA-P-089 Solitary fibrous tumor of the kidney M . Gajda1 , S . Harz1 , H . Wunderlich2 , K . Junker2 , M . Grimm2 , D . Katenkamp 1 , I . Petersen1 1 2 Institute of Pathology, Jena University Hospital, Department of Urology, Jena University Hospital Aims. Solitary fibrous tumors (SFT) are rare spindle cell neoplasms usually arising in the pleura. They have, however, also been reported at extrapleural locations. Urogenital localization is rare and to our knowledge, only 40 cases of SFT of the kidney have been described. Methods. Detailed clinical and histopathological review of a clinical case and review of the literature. Results. We report the case of a typical SFT of the right kidney in a 71-year-old woman. As part of a CT investigation, a large mass of the right kidney with suspicion thrombembolic compression and occlusion of the inferior vena cava was discovered. She underwent radical nephrectomy and lymphadenoctomy, adrenalectomy and interaortocaval lymph node dissection. The gross specimen included the kidney (12.8×6.6×7.5 cm), ureter and adrenal gland. Cut section showed a circumscribed pale brown mass measuring 9.6×7.4×5.2 cm tumor. The tumors consisted of bland-looking spindle cells arranged in short, ill-defined fascicles and storiform pattern with characteristic hemangiopericytoma-like blood vessels. Immunohistochemistry showed reactivity for vimentin, CD 34, BCL-2 protein and CD99. Immunohistochemical stains for cytokeratin, S-100, desmin, a-smooth muscle actin, RCC, EMA and CD 10 were negative. Ki67 labelling index exceeded 10%. Conclusions. The possibility of SFT should be considered in the differential diagnosis of a renal mass which consists of benign-looking spindle cells and hemangiopericytomatous blood vessels. Its diagnosis requires immunohistochemistry and awareness of its possible existence. 166 | Der Pathologe · Supplement 1 · 2012 Poster: Uropathologie II SA-P-090 Topotecan sensitizes renal cell carcinomas towards ABT-263 induced apoptosis S . Heikaus1 , V . Nitsche1 , S . Funke1 , H .E . Gabbert1 , C . Mahotka1 1Heinrich-Heine University Hospital, Institute of Pathology, Düsseldorf Aims. Renal cell carcinomas (RCCs) exhibit a marked resistance towards conventional chemotherapeutic regiments, thus making new therapeutic approaches necessary. So-called “targeted therapies” could be one strategy to overcome this broad resistance. Whereas “targeted therapies” with Kinase-Inhibitors like Sunitinib or Sorafenib are established in RCCs, therapies directly targeting apoptotic pathways are not validated. In this context, the BCL-2 inhibitor ABT-263 might be a promising new agent, aiming at the mitochondrial pathway of apoptosis, which is impaired in RCCs. We therefore examined the apoptotic effects of ABT-263 alone and in combination with Topotecan on the apoptosis of RCC cell lines. Methods. Cell culture, cell count, quantitative real-time detection PCR, Western Blot, Fluorescent Immunohistochemistry, Ribonuclease Protection Assay. Results. 1.) Expression of pro- and antiapoptotic BCL-2 family members was analysed in 7 RCC cell lines. Surprisingly, all cell lines expressed not only multiple antiapoptotic but also important proapoptotic BCL- 2 family members of all functional groups on the mRNA and protein level. 2.) ABT-263 and Topotecan induced apoptosis but not autophagy in RCCs. 3.) Sensitivity towards ABT-263 induced cell death inversely correlated with the expression of MCL-1. 4.) Topotecan downregulated MCL-1 protein expression in RCCs; in contrast, ABT-263 upregulated MCL-1 protein expression, whereas the expression of most of the other BCL-2 family members remained unchanged. 5.) Topotecan pretreatment weakly sensitized RCC cell lines towards ABT-263 induced apoptosis by synergistically activating the mitochondrial pathway of apoptosis. Conclusions. Inhibition of antiapoptotic BCL-2 family members by BCL- 2 inhibitors like ABT-263 might be a promising new approach in terms of a “targeted therapy” in RCCs. Furthermore, a combination with other chemotherapeutic agents can obviously enhance their proapoptotic effects. SA-P-091 Cadherin expression in different histological types of papillary renal cell carcinoma: a diagnostic tool C .L . Behnes1 , B . Hemmerlein1 , A . Strauss2 , H .-J . Radzun1 , F . Bremmer1 1 2 University of Göttingen, Institute of Pathology, University of Göttingen, Institute of Urology Aims. Cadherins constitute a family of transmembrane glycoproteins and include a variety of subtypes, of which E-cadherin has been widely studied. Functionally, the cadherins belong to the adhesion molecules and form cell-cell contacts. Furthermore they also play a role in the development of different organs and in tumorigenesis. The papillary renal cell carcinoma (RCC) is a rare tumor and is divided, based on histological criteria, into two subtypes, from which the type II papillary RCC do have a worse prognosis. There are no immunohistochemical markers for the distinction of these subtypes. Therefore we have examined the expression of four different cadherins in both subtypes of papillary RCC in order to find any diagnostically relevant differences. Methods. The expression of N-, P-, E- und KSP-Cadherin was deternined in 22 papillary RCC of histological type I and 18 papillary RCC of histological type II (n=40). The intensity of membranous and cytoplasmic immunhistochemical staining was semiquantitativly evaluated by a score from 0 to 3. To compare the data for significant differences we used the Wilcoxon-Test.
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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
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AG Oralpathologie DO-087 Detection
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DO-094 Do activated fibroblasts inf
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DO-101 Histopathological analysis o
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DO-108 Identification of potential
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Conclusions. In conclusion, 454 par
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subgroup of patients with B-Raf mut
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DO-002b Impact of terminologies in
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Methods. We performed MCPyV-FISH of
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FR-013 HPV-genotype distribution in
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Methods. Three different techniques
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(i.e. investment in equipment and e
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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
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
Page 136 and 137: Results. In 18 cases (79%) the caus
Page 138 and 139: FR-P-168 Autopsy findings in a 2-ye
Page 140 and 141: FR-P-174 MPGN-like glomerulonephrit
Page 142 and 143: Poster: Gynäkopathologie und Mamma
Page 144 and 145: SA-P-011 Genetic aberrations of pre
Page 146 and 147: Mechanismen, die eine Progression d
Page 148 and 149: internet server. A network of inter
Page 150 and 151: Methods. HE-gefärbte Schnittpräpa
Page 152 and 153: Conclusions. The newly released 450
Page 154 and 155: and desmoplastic reaction are diffe
Page 156 and 157: one patient revealed more than 9 mi
Page 158 and 159: situation, the V600E mutation in th
Page 160 and 161: SA-P-064 Evolution of molecular pat
Page 162 and 163: nic markers such as myf4 and MyoD1
Page 164 and 165: Conclusions. To our knowledge, this
Page 168 and 169: Results. The papillary RCC type II
Page 170 and 171: SA-P-098 Male infertility: assessme
Page 172 and 173: SA-P-104 Process oriented scientifi
Page 174 and 175: Conclusions. The IBDW offers a uniq
Page 176 and 177: L Lasitschka F. DO-046 Lehmann A. F
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