FR-P-129 Alpha-1-antitrypsin-PiZ-antibody ATZ11 recognizes von Willebrand factor (vWF): diagnostic and pathogenetic aspects K . Hiththetiya 1 , H . Zhou 1 , S . Steiner 1 , H .J . Hertfel<strong>der</strong> 2 , H .-P . Fischer 1 1 University Hospital Bonn, Institute of Pathology, Bonn, 2 University Hospital Bonn, Institute of Experimental Hematology and Transfusion Medicine, Bonn Aims. Antibody ATZ11 which is directed specifically against the mutated Alpha-1-antitrypsin PiZ will be tested on further specific binding sites independent of PiZ. The identity of the un<strong>der</strong>lying ATZ11-binding proteins will be analysed. Diagnostic und pathogenetic relevance of this specific cross-reaction will be discussed. Methods. Comparative immunhistochemical analysis, imunoelectronmicroscopic analysis, Western-blots of cultivated human vitelin cord endothelial cells and thrombocyte aggregates. Results. ATZ11-specific epitope is found immunohistochemically on megakaryocytes, platelets, endothelial cells of arteries, veins and some capillaries of normal human tissues. More extensive staining is found in portal vessels of end-stage liver cirrhoses. Neoexpression is found in sinusoidal endothelial cells of actively fibrosing liver diseases, especially in strongly progressive alcoholic steatohepatitis. Microvascular bed of hepatocellular carcinomas and hepatocellular adenomas remains unstained. The staining reactivity corresponds to that of von Willebrand factor (VWF) and P-Selectin. It is independent from the presence of hepatocellular AAT deposits of PiZ type and AAT genotype. The epitope can be detected in Weibel-Palade bodies (WPB) of human vitellin cord endothelial cells (HUVEC) and in the cytoplasm of patelets by immunoelectronmicroscopy. ATZ11-Western blotting of HUVEC and patelets visualizes a 240 kD molecule which is in the spectrum of the molecular weights of multimeric VWF. VWF deficient serum samples lack this ATZ11-binding molecule. Conclusions. Apparently ATZ11 binds to a conformation-dependent epitope of VWF which might reflect a special functional state of this protein. ATZ11 expression in sinusoids of actively fibrosing steatohepatitis highlights the possible role of VWF in sinusoidal occlusion by locally activated coagulation. Poster: Pneumopathologie FR-P-130 MAdL- a new specific marker for adenocarcinomas of the lung H . Schultz1 , S . Marwitz1 , B . Baron-Lühr1 , G . Zissel2 , C . Kugler3 , K .-F . Rabe3 , P . Zabel1 , E . Vollmer 1 , J . Gerdes1 , T . Goldmann1 1 2 Research Center Borstel, Borstel, University of Freiburg, Department for Pneumology, Freiburg, 3Hospital Großhansdorf, Großhansdorf Aims. Although the common immunohistochemical markers are well suitable for sub-differentiation a fraction of indistinct cases of NSCLC still remains, demanding upgrades of the panel by new markers. Methods. Here we report the generation and evaluation of a new monoclonal antibody denoted by “Marker of adenocarcinomas of the lung” (MAdL), which was raised against the cytoplasmatic fraction of primary isolated human alveolar epithelial cells type II. Results. Upon screening, one clone was identified as a marker for alveolar epithelial cells type II, alveolar macrophages and particularly adenocarcinomas of the lung. With an optimized staining procedure for formalin fixed tissues this antibody was evaluated together with the established markers TTF-1, SP-A, pro SP-B and Napsin A in a large-scale study on a series of 362 lung cancer specimens. MAdL displays a high specificity for adenocarcinomas of the lung together with a sensitivity of 76.5% and is able to provide independent additional diagnostic information to the established markers. Conclusions. We conclude that MAdL is a new lung specific marker for adenocarcinomas, which expands sub-differentiation in a notable portion of non-small cell lung cancers. FR-P-131 Pulmonary haptoglobin (pHp) can be used as a new specific marker for adenocarcinomas of the lung M . Abdullah1 , S . Marwitz1 , D . Kähler1 , H . Schultz1 , C . Kugler2 , P . Zabel3 , E . Vollmer 1 , T . Goldmann1 1 2 Research Center Borstel, Clin . & Exp . Pathology, Borstel, Hospital Großhansdorf, 3Research Center Borstel, Borstel Aims. There are novel chemo-therapeutic approaches which recently have been developed for NSCLC, known as a largely chemo-resistant tumour. Substantial differences have been shown between adenocarcinomas and squamous cell carcinomas with regard to the adequate therapeutic regimens. Therefore, sub-differentiation of NSCLC is currently getting more into focus and increasingly turning out to be a central element within therapeutic decisions. In this study we analyzed the expression of pulmonary haptoglobin (pHp) in human lung cancer tissues and compare it to common markers of adenocarcinomas. Methods. Immunohistochemistry and heat-induced antigen-retrieval were conducted. For detection, a one-step polymer-system was applied. 119 formalin-fixed, paraffin-embedded tumour tissues were immunohistochemically analyzed for expression of php, TTF-1, SP-A, SP-B and Napsin. Results. Pulmonary haptoglobin was expressed in 35 of 72 (48.6%) adenocarcinomas of the lung, [TTF-1 (79.1%), SP-A (51.3%), SP-B (48.6%) and Napsin (84.1%)]. Expression of pHp in squamous cell carcinomas (N=47) was absent. A proportion of cases exclusively express either pHp and Napsin (pHp+/Napsin+: 4.7%) or pHp and TTF-1 (pHp+/TTF-1+: 3.1%). 7.8–14% of the samples would have caused difficulties if the expression of pHp would not have been addressed. Conclusions. SP-A and SP-B are specific markers for adenocarcinomas with a limited sensitivity compared to TTF1; the same holds true for pHp. Therefore, the inclusion of pHp as an additional marker in the panel has serious impact on diagnostics and therapy. FR-P-132 The diagnostic value of cytokeratin 5/6, 14, 17, and 18 expression in human non-small cell lung cancer Y . Chen1 , T . Cui1 , L . Yang 1 , M . Mireskandari1 , T . Knösel1 , Q . Zhang1 , M . Pacyna- Gengelbach2 , I . Petersen 1 1 2 University Hospital Jena, Jena, University Hospital Charité, Berlin Aims. The constitution and expression patterns of cytokeratin filaments in human epithelial neoplasms are complex and distinctive. The aims of this study were analysis of the expression of cytokeratins and evaluation of their diagnostic application in human non-small cell lung cancer (NSCLC). Methods. mRNA expression of CK5, CK6, CK14, CK15, CK17, and CK19 was analyzed by Northern blotting. Protein expression of CK5/6, CK7, CK14, CK17, and CK18 was evaluated by immunohistochemistry on tissue microarrays. Results. Northern blotting showed that CKs were highly expressed in human bronchial epithelial cells and/or small airway epithelial cells. In NSCLC cell lines, the expression pattern of CKs was heterogeneous. In the survey of protein expression of CKs in 95 primary lung tumors, we found that CK5/6, CK14, and CK17 proteins were highly expressed in squamous cell carcinoma compared to adenocarcinoma (p=0.001, p=0.030, and p=0.001, respectively) and higher expression is significantly linked to lower grading (p=0.006, p=0.002, and p=0.001, respectively), while increased expression of CK7 and CK18 was observed in adenocarcinoma (p=0.001, respectively). Der Pathologe · Supplement 1 · 2012 | 125
Abstracts Conclusions. Our data suggest that CK5/6, CK7, CK14, CK17, and CK18 have diagnostic value in subclassification of NSCLC. FR-P-133 Malic enzyme expression in non-small cell lung cancer correlates with acetyl citrate expression and is associated with mediastinal lymph node metastasis A . Csanadi 1 , C . Otto 1 , N . Hörter 1 , A . Oser 1 , M . Donauer 1 , T . Plönes 2 , B . Passlick 2 , M . Werner 1 , G . Kayser 1 1 Institute of Pathology, University Hospital Freiburg, Freiburg, 2 Department of Thoracic Surgery, University Hospital Freiburg, Freiburg Aims. In contrast to normal human tissues malignant tumors utilize glucose mainly for the production of reductive equivalents and basic modules of nucleic acid, protein- and cell membrane synthesis, i.e. ribose, aminoacids and fatty acids. This metabolic shift results in pronounced production of lactate, known as the Warburg effect. Malic enzyme (ME) and acetyl citrate lyase (ACL) are two key enzymes involved in glucose metabolism and its linkage to fatty acid synthesis. We here analyzed the expression of these two enzymes in non-small cell lung cancer (NSCLC) and their association with local and systemic tumor disease. Methods. Protein expression in tissue multi arrays with a core diameter of 2 mm of 258 NSCLC patients was evaluated by immunohistochemical staining with ME (clone 3H5) and ACL (Cell Signaling 4331S). An H-score calculated by multiplication of the percentage of positive tumor cells with the predominant staining intensity (score 0 to 3) was used for nonparametric statistical analyses. Results. Expression of ME and ACL showed highly significant positive correlation (p
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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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- 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
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- Page 106 and 107: Results. Her2/neu status in TMAs an
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- Page 112 and 113: Methods. Biopsy specimens from 430
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- Page 116 and 117: FR-P-098 Immunohistological stainin
- Page 118 and 119: FR-P-104 Histopathological evaluati
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- Page 122 and 123: Conclusions. In primary imaging a g
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- Page 128 and 129: FR-P-136 The expression of central
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- Page 132 and 133: FR-P-149 Combination of Castleman d
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- 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
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- 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
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- Page 160 and 161: SA-P-064 Evolution of molecular pat
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L Lasitschka F. DO-046 Lehmann A. F
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