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

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DO-094 Do activated fibroblasts influence epidermal growth factor receptor (EGFR) inhibitor sensitivity in oral squamous cell carcinoma cells (OSCC)? P . Richter 1 , N . Neumann 2 , J . Schulte 3 , K . Schult 1 , S . Weisheit 4 , M . Franz 5 , O . Guntinas-Lichius 6 , C . Liebmann 4 , I . Petersen 1 , A . Berndt 1 1 Jena University Hospital, Institute of Pathology, Jena, 2 University Hospital Zurich, Institute of Surgical Pathology, Zurich, Switzerland, 3 Ludwig-Maximilian-University, Munich, Großhadern Medical Center/Department of Cardiac Surgery, München, 4 Friedrich Schiller University Jena, Institute of Biochemistry and Biophysics, Jena, 5 Jena University Hospital, Clinic for Internal Medicine I, Jena, 6 Jena University Hospital, Department of Otorhinolaryngology, Jena Aims. Although EGFR is involved in development of OSCC and EGFRinhibitor sensitivity could be shown in OSCC cell lines, a therapeutic benefit of an EGFR-inhibitor therapy can be observed only in a minority of patients. It was suggested that the carcinoma microenvironment have modulating effects on inhibitor sensitivity in vivo. One possible hypothesis is that carcinoma associated fibroblasts induce phenotype changes such as epithelial-mesenchymal transition (EMT) which are accompanied by alterations in EGFR signalling. Thus, the study was aimed at investigating the influence of growth factor activated fibroblasts on EGFRinhibitor sensitivity of OSCC in vitro applying Gefitinib. Methods. “Activated” fibroblasts were generated by stimulation of hTERT-BJ1 fibroblasts with TGFbeta1, PDGFAB, aFGF, and TGFbeta1/ aFGF, respectively. They were characterized with regard to proliferation, expression of fibroblast markers, activation of EGFR signalling, and the capability to induce OSCC cell invasion as well as their Gefitinib sensitivity using immunohistochemistry, western blotting, rtRT-PCR, MTT test and Boyden chamber assay. Furthermore, Gefitinib sensitivity was evaluated in different OSCC cell lines by MTT test. The impact of TGFbeta1 and TGFbeta1/aFGF activated fibroblasts on EGFR inhibitor sensitivity was assessed by pre-culturing of OSCC cells in fibroblast conditioned media. Results. In vitro activated fibroblasts showed a strong upregulation of ASMA and fibronectin due to stimulation with TGFbeta1. PDGFAB stimulation induced proliferation with up-regulation of EGFR and pAKT. aFGF and TGFbeta/aFGF stimulation resulted in an intermediate phenotype. TGFbeta1 stimulated fibroblasts exhibited the highest capability to induce invasion in the OSCC cell line PE/CA-PJ15 with upregulation of N-cadherin. Interestingly, activated fibroblasts differed in their Gefitinib sensitivity (TGFbeta-stim.=”low” and PDGFAB stim.=”high”). OSCC cell lines tested so far show a different Gefitinib sensitivity. Furthermore, pre-culturing in fibroblast conditioned medium leads to a partial reversibility of the Gefitinib effect. Conclusions. Results indicate that: 1) EGFR inhibition by Gefitinib affects OSCC cells as well as activated stromal fibroblasts, 2) the different Gefitinib sensitivity of fibroblast phenotypes may lead to a selective accumulation of myofibroblasts during treatment, and 3) OSCC cell sensitivity is modulated by stromal fibroblasts. DO-095 Evaluation of post-transplant lymphoproliferative diseases (PTLD) with manifestation in the oral cavity C . Tiede1 , B . Maecker-Kolhoff 2 , H . Kreipe1 , K . Hussein1 1 2 Hannover Medical School, Institute of Pathology, Hannover, Hannover Medical School, Hannover Aims. Inspection of the oral cavity can be easily performed in transplanted patients with an oral tumour mass and suspected Epstein-Barr virus (EBV)-associated post-transplant lymphoproliferative disease (PTLD). We aimed to evaluate the main sites of manifestation and the morphological subtypes of PTLD in the oral cavity. Methods. Evaluation of histomorphology and clinical data on early lesion, polymorphic, and monomorphic PTLD. Total cohort of 212 patients (median age 9 years, range 0.5–70 years, 57% males/43%females, 75.5% children/24.5% adults). Results. Oral cavity PTLD manifestation was found in 61/212 patients (29%): 42/61 early lesion PTLD (20%), 12/61 polymorphic PTLD (6%) and 7/61 monomorphic PTLD (3%). Tonsils were the most frequent site of manifestation (n=57/61, 93%) including early lesion PTLD (n=42/57, 74%), polymorphic PTLD (n=12/57, 21%) and monomorphic B cell PTLD (n=3/57, 5%). Other localisations were gingiva (n=2/61, 3%; EBV+ plasmocytomas), maxillary bone (n=1/61, 1.5%; EBV+ plasmocytomas) and larynx (n=1/61, 1.5%; EBV-T-cell PTLD). Conclusions. Tonsils are the main site of PTLD manifestation in the oral cavity and comprise mainly benign early lesion PTLD and polymorphic PTLD. Oral cavity monomorphic PTLD is rare and is located outside of the tonsils in a considerable proportion (n=4/7, 57%) of cases. DO-096 Non-sebaceous lymphadenoma of salivary glands: proposed development from intraparotid lymph nodes and risk of misdiagnosis C . Weiler1 , A . Agaimy2 , P . Zengel3 , J . Zenk4 , T . Kirchner1 , S . Ihrler5 1 2 Ludwig Maximilian University, Institute of Pathology, München, University Hospital Erlangen, Institute of Pathology, Erlangen, 3Ludwig Maximilian University, Head and Neck Surgery, München, 4University Hospital Erlangen, Head and Neck Surgery, 5Laboratory for Dermatohistology and Oral Pathology, München Aims. Non-sebaceous lymphadenoma (NSLA) is a rare benign salivary gland tumour composed of lymphoid and epithelial components. Definitionally, the epithelial component lacks sebaceous differentiation and, instead, displays a wide range of histological differentiation. In this study, we have collected 9 cases of NSLA to characterize their histological and immunohistochemical profile. Methods. The samples were histologically reviewed, and immunohistochemical stains for CK5/6, CK7, CK14, CK18, p63, and Ki67 performed. Patients were 6 males and 3 females (mean age, 50 years). Results. All tumours were located in the parotid gland and showed intimate intermingling of lymphoid tissue with islands or strands of epithelium with a wide spectrum of histological differentiation. The immunohistochemical profiles mirrored the epithelial differentiation; hence, areas with basaloid or lymphoepithelial differentiation strongly expressed CK5/6, CK14, and p63, while areas with ductal differentiation showed strong positivity for CK18/CK7 and CK5/6/CK14/p63 in luminal and basal cell layers, respectively. A hilus structure with salivary inclusions or D2-40 (podoplanin) positive marginal sinus were identifiable in 4 and 9 of the cases, respectively, confirming origin within intra-/periparotid lymph nodes. Six cases were initially misdiagnosed as other benign (n=4) or malignant tumours (n=2). Conclusions. Our study on the largest series of NSLA reported to date provides strong evidence that NSLA belongs to the group of salivary gland tumours that pathogenetically develop from embryonic salivary gland inclusions in intra-/periparotid lymph nodes. Knowledge of the wide histological spectrum of this rare and presumably underreported tumour is important in order to avoid misdiagnosis, particularly as malignant tumour. Der Pathologe · Supplement 1 · 2012 | 37
Abstracts DO-097 Cytokeratin-positive epithelioid angiosarcoma presenting in the tonsil: a diagnostic challenge A . Agaimy 1 , H . Kirsche 2 , S . Semrau 3 , H . Iro 2 , A . Hartmann 1 1 Friedrich-Alexander University of Erlangen, Institute of Pathology, Erlangen, 2 Friedrich-Alexander University of Erlangen, Department of Otorhinolaryngology, Head and Neck Surgery, Erlangen, 3 Friedrich-Alexander University of Erlangen, Department of Radiation oncology, Erlangen Aims. The majority of malignant neoplasms of the head and neck represent squamous cell carcinomas while sarcomas are rare in this anatomic region. Primary oral cavity sarcomas are exceedingly rare and may pose a great diagnostic challenge. Methods. A 71-year-old woman without previous history of malignancy or radiation to the head and neck presented with an antibiotic-refractory diffuse painful swelling of the right tonsil necessitating tonsillectomy. Within months the patient underwent surgical resection of multiple bleeding intraoral and gastrointestinal metastases. She is currently alive with disease 9 months from diagnosis. Results. Histological evaluation revealed subtotal replacement of the right tonsil by a high-grade epithelioid neoplasm displaying extensive ulceration, necrosis and primitive vasoformation. Immunohistochemistry showed strong/diffuse expression of pancytokeratin (CK) antibodies KL-1 and Lu5, CK8, CK18, CK19, vimentin, CD31, ERG and FLI-1. High molecular weight cytokeratins (CK5, 34ß12), CK7, CK13 and CK20 were not expressed. Conclusions. To our knowledge, this case represents the first well documented primary epithelioid angiosarcoma of the tonsil. The strong cytokeratin expression in epithelioid angiosarcomas represents a diagnostic pitfall. Thus, awareness of this rare and highly aggressive neoplasm is necessary for distinguishing it from poorly differentiated and acantholytic squamous cell carcinoma and diffuse large cell lymphoma. DO-098 Lipomatous neoplasms of the salivary glands. A series of 23 cases with emphasis on oncocytic lipoadenoma and sebaceous differentiation A . Agaimy1 , B . Märkl2 , H . Arnholdt2 , J . Zenk3 , V . Bonkowsky4 , M . Michal5 , A . Skalova5 , A . Hartmann1 , S . Ihrler6 1Friedrich-Alexander University of Erlangen, Institute of Pathology, Erlangen, 2Augsburg Clinic Center, Augsburg, 3Friedrich-Alexander University of Erlangen, Department of Otorhinolaryngology, Head and Neck Surgery, Erlangen, 4Nürnberg Clinic Center, Department of Otorhinolaryngology, Head and Neck Surgery, Nürnberg, 5Charles University, Medical Faculty Hospital, Department of Pathology, Pilsen, Czech Republic, 6Ludwig Maximilian University, Munich, Department of Pathology, München Aims. Lipomatous tumors of salivary glands are rare and have been the subject of rare case reports in the literature. Accordingly, their morphologic spectrum and clinicopathological features from a consecutive case series have not been studied. Methods. We collected 23 fatty tumors from consecutive surgical pathology files at four large hospitals (n=17) and from consultation files of two centers (n=6). Fat-containing pleomorphic adenoma and lipomatous myoepitheliomas were excluded. Results. There were 15 males and 8 females aged 18–89 yrs (mean, 55 yrs). Most tumors (n=21) originated in the parotid gland. Two affected the submandibular gland. Histologically, the tumors could be categorized into three groups: ordinary lipoma (n=16; 70%), oncocytic lipoadenoma (n=4) and non-oncocytic adenolipoma/sialolipoma (n=2). Ordinary lipomas were either completely intraglandular or they have been submitted as a lipomatous nodule containing minor foci of residual atrophic serous acini at the periphery of the lipoma beneath the capsule. None of the lipomas contained sebaceous elements or oncocytic cells. The less 38 | Der Pathologe · Supplement 1 · 2012 common oncocytic lipoadenoma (synonym: oncocytic sialolipoma) had a fatty component ranging from 10% to 95% of the lesion that was usually interspersed between the oncocytic acini. Sebaceous islands were found in three of the four cases. The oncocytes showed either diffuse solid sheets with a lobular architecture interrupted by scattered adipocytes or were scattered between plentiful fatty tissues. The two non-oncocytic adenolipoma (synonym: non-oncocytic sialolipoma) were predominantly fatty (70–80%) and prominently lobulated. They displayed a biphasic pattern with serous tissue diffusely distributed between the fatty components. One lesion showed foci of sebaceous metaplasia. Conclusions. Lipomatous tumors of the salivary glands are rare and most represent intraglandular ordinary lipomas that are otherwise similar to their soft tissue and cutaneous counterparts. While fairly absent in ordinary salivary lipomas, sebaceous differentiation seems to be a common feature of oncocytic lipoadenoma and non-oncocytic sialolipoma. Lipomatous lesions of the salivary glands do not seem to be association with other significant salivary gland pathology or to carry a risk of malignant degeneration. Although lipomatous components in these lesions might derive from intraglandular adipose tissue, the pathogenesis of the oncocytic and sebaceous elements (metaplastic vs. neoplastic) remains unclear. AG Herz- und Gefäßpathologie DO-100 microRNA-143 is essential in arteriogenesis K . Troidl1 , G . Jung1 , C . Troidl2 , W . Schaper 1 , T . Schmitz-Rixen3 1Max-Planck-Institute for Heart and Lung Research, Bad Nauheim, 2 3 Kerckhoff Heart Centre, Bad Nauheim, Goethe University, Frankfurt Aims. Arteriogenesis – the growth of pre-existing collateral arterioles to functional arteries – is triggered by increased fluid shear stress (FSS). MicroRNAs (miRNA) are implicated in post-transcriptional regulation of gene expression. A FSS-induced signature pattern of miRNAs during collateral growth might influence signal transduction of the physical stimulus into a cellular response. We investigated the involvement of miRNAs in arteriogenesis in a rat model of chronically elevated FSS in collateral arteries. Methods. 6 sprague dawley rats were subjected to femoral artery ligature (FAL). A side-to-side anastomosis distal to the ligature was created between the femoral artery and the accompanying vein, which leads to chronically elevated FSS inside the collaterals. Following dissection of collateral tissue 7 d after surgery, miRNA was isolated and an expression profile was generated by microarray analysis. Differential expression was confirmed by qRT-PCR. Cellular localization of selected miRNAs was assessed by in situ hybridisation combined with immunostaining. By local blockage of specific miRNAs in mouse collaterals we analyzed their functional involvement in arteriogenesis. Results. Growing collaterals showed a significant up-regulation of 6 miRNAs when compared to sham operated controls. miR-143, miR-195, and miR-24 were localized in the media of growing collaterals. miR-24 is also expressed in the FSS-stimulated endothelium. Blockage of miR-143 led to severe impairment of arteriogenesis. Conclusions. These data indicate that miRNas are involved in arteriogenesis. miR-143 belongs to a cluster which has been assigned to the phenotypic switch of smooth muscle cells. We identified a functional implication during vascular remodeling. Targeted modulation of this miRNA in vivo suggests new treatment options in improvement of collateral growth.
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 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
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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
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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
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FR-P-136 The expression of central
Page 130 and 131:
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
Page 140 and 141:
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
Page 150 and 151:
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
Page 160 and 161:
SA-P-064 Evolution of molecular pat
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nic markers such as myf4 and MyoD1
Page 164 and 165:
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
Page 172 and 173:
SA-P-104 Process oriented scientifi
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Conclusions. The IBDW offers a uniq
Page 176 and 177:
L Lasitschka F. DO-046 Lehmann A. F
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