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

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Methods. We performed MCPyV-FISH of formalin fixed and paraffin embedded (FFPE) MCCs (n=62) on tissue microarrays (TMAs), determined the hybridization patterns and correlated these with qPCR data on the basis of a determined cut-off. MCPyV-FISH was established using the MKL-1 cell line which harbors integrated copies of MCPyV DNA. For MCPyV-qPCR a LT primer pair (Becker et al., 2009) was used on whole tissue sections. Results. MCPyV-FISH on FFPE MKL-1 cells revealed punctate signals compatible with viral integration. The MCPyV-FISH positive MCC cores (76%) mainly revealed two different signal patterns: a punctate pattern (85%) which correlated with a moderate relative viral abundance and in some areas the punctate pattern was combined with a diffuse pattern (15%) indicating the episomal presence of the virus which is linked to viral replication. A mixed hybridization pattern was associated with very high qPCR values. Comparing MCPyV-FISH and qPCR data the results highly correlated (83%) with the MCPyV positive evaluated group, whereas the negative group showed a concordance of 93%. The mean of the qPCR values of all MCPyV positive cores differed significantly from the negative cores (p=0.0076). In some tumor areas of one and the same patients the FISH signals were heterogeneous in intensity, pattern and nuclear localization. Conclusions. A strong correlation between MCPyV FISH and the relative MCPyV abundance by qPCR was detected. Thus, while presence of MCPyV can be verified by qPCR, the quality of the presence can be visualized by MCPyV specific FISH analysis. In this regard, MCPyV qPCR and MCPyV FISH are important complementary tools to gain maximum biological information of the presence of MCPyV in MCC and thus to further elucidate MCPyV related carcinogenesis. FR-007 A novel BRAF mutation in a patient with metastatic melanoma R . Schneider-Stock 1 , L . Heinzerling2 , E . Kämpgen2 , M . Erdmann2 , P . Keikavoussi2 , A . Agaimy1 , A . Hartmann1 , G . Schuler2 1University of Erlangen-Nuremberg, Institute of Pathology, Erlangen, 2University of Erlangen-Nuremberg, Department of Dermatology, Erlangen Aims. BRAF mutations in melanoma have been identified as a new target for therapy. The V600E mutation is found in 50–68% of malignant melanomas and can be specifically treated with e.g., the BRAF inhibitor PLX4032 now registered as Vemurafenib. We describe a patient with a metastasized nodular melanoma on the right lumbar region which was excised two years before but had already spread to the inguinal lymph nodes. Subsequently, the patient developed multiple metastases of the brain, metastases of the mediastinal, cervical, retroperitioneal, retrocrural, mesenterial, paraaortal and interaortocaval lymph nodes, in the liver, the stomach and the intestines. Previous therapy included lymphadenectomy, radiation therapy, hyperthermia, radiochemotherapy with temozolomide, sorafenib, fotemustine and paclitaxel/carboplatin. Despite these attempts he showed progressive disease and inclusion into a BRAF inhibitor study was considered. Thus the tumor was sent for mutation analysis. Methods. Formalin-fixed and paraffin-embedded tumor sample was used for the extraction of genomic DNA. Mutational analysis was carried out by Pyrosequencing and for confirmation by ABI capillary sequencing of exon 15 of BRAF. Results. In this melanoma patient a new complex mutation was found in BRAF with base substitution of a valine residue at position 600 for glutamic acid (GTG GAA) and deletion of codon 601 (p.V600EK601del; c.1799_1801del3). With this mutation the patient did not qualify for the BRAF inhibitor study. The clinical course of the patient was rapidly progressive with various acute complications (renal insufficiency, ileus) and the patient deceased only 2 months after analysis of the mutation. Conclusions. The V600E mutation constitutively activates RAF/MEK signaling, a major driver of carcinogenesis in various malignancies. Other rather rare mutations like V600K, V600R or V600D might also cause this constitutive activation and are discussed to be correlated with a yet more aggressive behaviour. It is unclear whether the new mutation described in this case can be considered for targeted BRAF inhibitor therapy. FR-008 The aid of immunohistochemistry in differential diagnosis between benign and malignant phenotype of difficult melanocytic lesions T . Papadopoulos1 1Klinikum Nürnberg, Institute of Pathology, Nürnberg Aims. A panel of biological markers differentially expressed in common nevi, dysplastic nevi, Spitz nevi and malignant melanomas are introduced providing a potential tool to differentiate benign from malignant phenotype in difficult melanocytic lesions. The panel includes Cyclin D1, p16, p21 and p53. Methods. Cyclin D1 is markedly expressed in radial growth phase malignant melanomas but is negative in common nevi and in the deepest part of vertical growth phase melanomas as well. The cell cycle inhibitor p16 is positive in benign nevi and radial growth phase melanomas but becomes often negative as malignant melanoma progresses to the vertical growth phase. The cell cycle inhibitor p21 is positive in radial growth phase melanomas and in thin vertical growth phase melanomas but becomes negative in thick malignant melanomas. p21 is negative in common melanocytic nevi. Both cell cycle inhibitors p16 and p21 are upregulated in Spitz nevi and Spitzoid nevi. Finally, p53 is negative or positive at a very low level in melanocytic nevi. Its expression increases with tumor progression from dysplastic nevus to radial growth phase malignant melanoma and vertical growth phase malignant melanomas. Conclusions. This presentation demonstrates characteristic expression patterns of the above mentioned panel that may enable pathologists to differentiate benign from malignant melanocytic lesions even in cases when morphology by itself may not allow a clear classification of the melanocytic lesion. Notiz an die Gutachter des Abstracts: Der Abstract wurde nach Rücksprache und auf Wunsch von Prof . Meister (München) eingereicht . Vorgesehen ist ein etwa 15- bis 20-minütiger Vortrag, quasi als Review für die Immunhistochemie unklarer melanozytärer Läsionen . AG Dermatopathologie und AG Zytopathologie II – Endokrine Themen FR-009 Epidermal growth factor receptor mutation analysis in pleural effusions of advanced non-small cell lung cancer patients: When only cells are available A . Zimpfer1 , B . Schneider1 , A . Polak1 , A . Bier2 , J . Kölbel1 , J .C . Virchow2 , A . Erbersdobler1 1 2 University of Rostock, Institute of Pathology, Rostock, University of Rostock, Rostock Aims. Epidermal growth factor receptor (EGFR) mutations are associated with an improved clinical outcome due to response to tyrosine kinase inhibitors in patients with non-small cell lung cancer (NSCLC). The overwhelming majority of bronchial cancer is diagnosed on often very limited tumor material which is also requested for secondary mutational analysis. This study assessed the feasibility of using PCR and gene-sequencing to screen for (EGFR) mutations in pleural effusions of advanced NSCLC patients. Der Pathologe · Supplement 1 · 2012 | 49
Abstracts Methods. EGFR mutation analysis was performed in 16 cases of malignant pleural effusions in lung cancer patients. 6 patients were male (range 48–77 years, median 60.5 years) and 8 were female (range 66–86 years, median 77.5 years). In 1 case 3 pleural effusion specimens of 1 male patient were examined. Precipitations of fibrin in pleural effusions were subjected to cell block technique. Tumor cell enrichment was performed in 2/16 cases. The DNA was extracted and exons 18–21 of EGFR amplified. Sequence analysis of the PCR products was performed using an Applied Biosystems 3500 system. Results. Molecular analysis of all EGFR target sequences was achieved in 14 of 16 (87.5%) cases. EGFR mutations were identified in 3/14 (21.4%) of fully evaluated cases (1 pleomorphic carcinoma and 2 NSCLC). Two cases carried a deletion in exon 19 (K745-A750) and the third case a point mutation in exon 20 (V769M, G779F). Conclusions. EGFR mutations in pleural effusions from advanced NSCLC patients can be detected and characterised by PCR and gene sequencing. Thus, further and costly procedures for tissue retrieval would be unnecessary in some cases. The availability of EGFR mutation testing of cytological specimen is a valuably tool in the concerted cytologic/histologic diagnosis of NSCLC and help to spare precious tissue material for additional tests. FR-010 Significant increased detection for cervical dysplasia using the ThinPrep Integrated Imager G . Richter1 , U . Hahlbohm1 , D . Teschner1 1Institute of Pathology Dr . Richter, Hameln Aims. The liquid based cytology using the ThinPrep PAP test is a standardised method of smear testing and cell processing that was developed in the USA. The ThinPrep Integrated Imager has been available for computer assisted liquid based cytology since autumn 2009. This presentation compares the results of the ThinPrep Integrated Imager of 2010 with the so called normally produced liquid based cytology in 2007. Methods. As a DIN/ISO17020 accredited Institute we have been carrying out the conventional PAP smear test and since 2000 also the liquid based cytology using the ThinPrep PAP test. Since November 2009 the liquid based cytology is carried out computer assisted. Results. In 2007 we manually evaluated 3582 ThinPrep PAP tests of which 98% were of an inconspicous PAP group I or II; 1.6% of PAP group IIW; 0.03% of PAP group III; 0.5% of PAP group IIID; 0.14% of PAP group IVa; 0.03% of PAP group IVb. In 2010 we evaluated 4408 ThinPrep PAP tests using the Integrated Imager of which 94% were of an inconspicuous PAP group I or II; 3.4% of PAP group IIW, 0.05% of PAP group III; 2.6% of PAP group IIID; 0.2% of PAP group IVa and 0.02% of PAP group IVb (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 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 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 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
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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 166 and 167:
SA-P-085 Expression of the eukaryot
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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96. Jahrestagung der Deutschen Gesellschaft für Pathologie e. V ...

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