immature granulopoiesis showed a strong ID3 protein expression, the more mature granulocytes only displayed a minimal reactivity. In contrast, erythropoiesis remained negative for ID2/3 (p
Abstracts ray-based expression profiling in 468 tissue samples from 25 healthy organs from more than 210 patients. Results. We found that CD317 protein was expressed to varying degrees in all organs tested and detected in a number of specialized cell types, including hepatocytes, pneumocytes, ducts of major salivary glands, pancreas and kidney, Paneth cells, epithelia, Leydig cells, plasma cells, bone marrow stromal cells, monocytes, and vascular endothelium. Although many of these cell types are in vivo targets for pathogenic viruses, restriction by CD317 or virus-encoded antagonists has been documented in only some of them. Limited cell type-dependent co-expression of CD317 with the IFN biomarker MxA in vivo and lack of responsive stimulation in organ explants suggest that interferons may only partially regulate CD317. Conclusions. This in vivo expression profiling sheds light on the biology and species-specificity of CD317, identifies multiple thus far unknown interaction sites of viruses with this restriction factor, and refutes the concept of its restricted constitutive expression and primary IFN inducibility. CD317’s widespread expression calls into question its suitability as a target for immunotherapy. DO-047 Frequent detection of the Merkel cell polyomavirus in B-lymphocytes: implications for non-Hodgkin lymphomagenesis? D . Rennspiess1 , A . Haugg1 , J . Beckervor<strong>der</strong>sandforth1 , A .K . Kurz2 , R . Plusquin1 , G . Cathomas3 , C . Wendtner4 , E .-J . Speel1 , H . Kvasnicka5 , A . zur Hausen1 1Maastricht University Medical Center, Department of Pathology, Maastricht, Netherlands, 2University Hospital Aachen, Department of Internal Medicine IV, Aachen, 3Kantonsspital Liestal, Institute of Pathology, Switzerland, 4University Hospital Cologne, Department I of Internal Medicine, Köln, 5University Hospital Frankfurt, Institute of Pathology, Frankfurt Aims. The recent discovery of the Merkel cell polyomavirus (MCPyV) in Merkel cell carcinomas (MCC) also had an important impact on the well established epidemiological association of CLL/SLL with MCC. We have recently demonstrated the presence of MCPyV DNA in highly purified CD5+/CD19+ CLL cells. Meanwhile, the presence of MCPyV DNA in CLL/SLL cells has been independently demonstrated by two other groups reporting MCPyV-DNA in approx. 21–33%. In addition, we were able to demonstrate MCPyV integration by fluorescence in situ hybridisation (FISH). Here we extended our analyses to different types of non Hodgkin lymphomas (NHL) as well as to non neoplastic reactive follicular lymph nodes for the presence of MCPyV by FISH and/or MCPyV DNA PCR. Methods. DNA PCR was carried out on 8 formalin-fixed and paraffin embedded SLL cases and 1 DLBCL case and on 39 reactive lymph nodes as previously described. On these and on a tissue microarray (TMA) containing CLL/SLL (n=43), MZL (n=44), FL (n=40), MALT (n=47), DLBCL (n=32), and T cell lymphomas (n=19) MCPyV FISH was performed. Results. MCPyV DNA was detected by PCR in 6 of the 8 SLL cases and in 13 of the 39 reactive lymph nodes. By MCPyV FISH sharply punctate dots – compatible with viral integration – were identified in 29% (n=15/51) of CLLs, in 9% (n=4/45) of MZL, in 35% (n=14/40) of FL, in 15% (n=7/47) of MALT, and in 18% (n=6/32) of DLBCL. All T cell lymphomas were MCPyV negative. Of interest, small clusters of MCPyV DNA positive B cells were detected in the follicle centres of the reactive lymph nodes. These hybridization signals were punctate and multiple, and some of them revealed a diffuse hybridization pattern. Conclusions. MCPyV FISH confirms our previous data on the integrated presence of MCPyV in CLL. Other B-cell NHL might be associated with the presence of integrated MCPyV. The finding of small clusters of follicular B-cells harbouring integrated MCPyV DNA is suggestive for an early and rather common MCPyV infection of premature B-cells which normally – during the process of follicular B-cell maturation – are eliminated. MCPyV-positive follicular B-cells which are not eliminated, thus not recognised as “foreign”, are likely to be the reservoir of cells 26 | Der Pathologe · Supplement 1 · 2012 which during a long-term transformation process by an accumulation of oncogenic mutations or deletions turn into a NHL cell. Functional studies concerning MCPyV and lymphomagenesis are ongoing in or<strong>der</strong> to elucidate a possibly un<strong>der</strong>lying etiopathogenic role for MCPyV in NHL lymphomagenesis. DO-048 The majority of immunohistochemically BCL2 negative FL grade I/ II carry a t(14;18) with mutations in exon 1 of the BCL2 gene and can be identified with the BCL2 E17 antibody I . Bonzheim1 , R . Baumann1 , P . Adam1 , F . Fend1 , L . Quintanilla-Martinez 1 1University Hospital Tübingen, Institute of Pathology and Neuropathology, Tübingen Aims. Follicular lymphoma (FL) is characterized by the translocation t(14;18)(q32;q21) resulting in constitutional overexpression of the antiapoptotic protein BCL2. However, 10–15% of FL grade I/II remain negative in the immunohistochemical (IHC) staining for BCL2. The aims of this study were: 1) to investigate the incidence of IHC BCL2 negative FL grade I/II diagnosed at our institution, 2) to analyze BCL2 IHC negative FL with the alternative BCL2 antibody (clone E17) and perform FISH analysis for the t(14;18), and 3) to elucidate the molecular mechanism of immunohistochemical BCL2 negativity. Methods. FL grade I/II diagnosed between 01/2005 and 08/2011 at the Institute of Pathology of the University of Tübingen were included in the study. All cases were stained with the standard BCL2 antibody (clone 100D5; DCS). BCL2 negative cases were subsequently stained with the BCL2 antibody, clone E17 (Zytomed) and analyzed by FISH using a BCL2 break-apart probe (LSI BCL2 BAP, Vysis). Exon 1 of the BCL2 gene, where the epitope of the standard BCL2 antibody resides, was amplified and sequenced. Results. 23 (9.6%) of the 240 identified cases of FL grade I/II were negative with the standard BCL2 antibody. Of these, 13 cases (57%) were positive for the E17 antibody and 10 cases (43%) remained negative. All E17 positive cases showed a BCL2 break by FISH analysis, indicative of a t(14;18), whereas the E17 negative cases lacked BCL2 alterations. Two of the E17 negative cases carried a BCL6/IGH translocation. Sequencing of BCL2 exon 1 revealed missense point mutations resulting in amino acid substitutions in all 9 analyzable E17-positive cases, with a hot spot around codon 144. Conclusions. The incidence of immunohistochemically BCL2-negative FL grade I/II in our series is comparable to published data. The E17 antibody reveals the presence of BCL2 protein undetectable with the standard antibody due to exon 1 missense mutations in the majority of BCL2 “negative” FL grade I/II and correlates with the presence of the t(14;18). The molecular pathogenesis of the BCL2 (E17)- and t(14;18) negative FL grade I/II remains to be determined. DO-049 Follicular lymphoma with prominent mantle zones – a FICTION analysis P . Kosmidis1 , P . Adam1 , I . Bonzheim1 , L . Quintanilla-Fend1 , P . Bauer2 , M . Scharpf1 , T . Henopp1 , F . Fend1 1Eberhard-Karls-University, Institute of Pathology and Neuropathology, Tübingen, 2Eberhard-Karls-University, Institute of Human Genetics, Tübingen Aims. Follicular lymphoma (FL) is characterized by the recurrent translocation t(14;18), resulting in BCL2 protein overexpression. Most cases show an indolent clinical course, which in part may be a result of the influence of the complex tumor microenvironment of FL. Involvement of different lymph node compartments may indicate a biologically more advanced lymphoma, whereas restriction of neoplastic cells to germinal centers might represent earlier disease stages. We have therefore exami-
- 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 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
- 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
- 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 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