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

cosa and in the periarterial tissue. These cells do not display an expression
of SMA or SMM. All analysed malignant tumors demonstrate a loss
of stromal CD34 expression and a phenotype change from CD34+SMA-
SMM- fibrocytes to CD34-SMA+SMM+ myofibroblasts.
Conclusions. Primary and secondary malignant tumors located in the
lung and pleura display a constant stromal phenotype change from
CD34+SMA-SMM- fibrocytes to CD34-SMA+SMM+ myofibroblasts.
This phenomenon is stereotypical for all organs (i.e. pancreas, mamma,
cervix) analysed this far. Furthermore the comparison with in situ carcinomas
indicates the major role of the loss of stromal CD34 expression
in local tumor invasion.
FR-P-143
Cytology-based diagnosis of malignant mesothelioma on behalf
of the German Social Accident Insurance Institution
S . Biesterfeld1 1Heinrich Heine University, Department of Cytopathology, Düsseldorf
Aims. Histology usually represents the gold standard for the diagnosis
of malignant mesothelioma. However, sometimes cytological material,
mainly as pleural fluid, is available solely. Here, we discuss those four
cases which were investigated in our institution in 2010 during the estimation
procedure on the reduction in earning capacity according to the
occupational diseases ordinance (No. 4105: “asbestos-induced malignant
mesothelioma”), ordered by the German Social Accident Insurance Institution.
Methods. In addition to routine cytology, we applied immunocytochemistry
(calretinin, berEP4, HEA125, TTF-1), DNA image cytometry, Ag-
NOR-analysis and FisH (at the region 9p21) and interpreted the results
considering the clinical and occupational history.
Results. In one of the four cases, a malignant effusion due to metastatic
lung cancer was diagnosed. In two cases, the diagnosis of an epitheloid
malignant mesothelioma was made. The fourth case in our opinion revealed
reactive changes only, and manifest tumor cells of a malignant
mesothelioma could not be detected. In all four cases, our interpretation
has been agreed by the Statutory Accident Insurance Funds. The first
three cases were accepted as asbestos-associated occupational diseases,
while the forth case was rejected initially. However, this patient meanwhile
has died, and the autopsy findings, taken in another institution,
led to the acceptance of asbestos-associated malignant mesothelioma.
Conclusions. Cytology-based tumor diagnosis is a useful and reliable
approach in those cases of asbestos-associated tumors in which no histology
can be obtained. The acceptance of cytological diagnoses by the
German Social Accident Insurance Institution enables to come to a conclusive
during the remaining lifetime of those patients by shortening the
procedure to estimate the reduction in earning capacity.
FR-P-144
Transcriptome analyses and validation of the targets reveal
impact of the TGF-β pseudoreceptor BAMBI for COPD
S . Marwitz1 , D . Drömann2 , J . Rupp3 , K . Rohmann3 , S . Osbahr3 , A .-J . Ulmer1 ,
K . Röschmann1 , M . Abdullah1 , H . Schultz1 , E . Vollmer1 , P . Zabel2 , K . Dalhoff2 , T .
Goldmann1 1Research Center Borstel, Leibniz Center for Medicine and Biosciences,
Borstel, 2University Clinic Schleswig-Holstein Campus Lübeck, Medical Clinic
III, Lübeck, 3University Clinic Schleswig-Holstein Campus Lübeck, Institute of
Medical Microbiology and Hygiene, Lübeck
Aims. Transforming Growth Factor beta (TGF-β) signaling events control
a variety of different cellular reactions and are involved on both,
physiologic and pathologic processes. Epithelial as well as cells of the
immune system respond to TGF-β signals throughout the body. The influence
of TGF-β signals in non-malignant lung diseases are up to date
critically discussed and infection-triggered tissue inflammation as well
as remodeling seems to inhabit a central role in the exacerbation and
pathogenesis of chronic obstructive pulmonary diseases (COPD). Infection-triggered
tissue inflammation and remodeling requires tight regulatory
events in the interplay of epithelial and immune cells and TGF-β
is one of the major cytokines involved.
Methods. Ex vivo infected human lung tissues with Non-Typeable Haemophilus
influenzae (NTHI) were subjected to transcriptome analysis.
Infection of lung tissue was verified by RNA in situ hybridization targeting
NTHI mRNA. Pathway analysis of different TGF-β members was
conducted on RNA and protein level and compared to COPD tissues.
Expression and secretion of pro-inflammatory molecules (IL-8, TNF-α)
were analyzed by means of western blotting and ELISA.
Results. 38% of COPD patient samples showed positivity for NTHI on
RNA level in contrast to 0% of controls. Transcriptome based pathway
analysis showed no significant changes of TGF-β receptors as well as cytokines
in contrast to a strong up regulation of Bambi in ex vivo infected
lung tissues as well as in COPD tissues. Bambi was found to be expressed
on alveolar macrophages as well as alveolar epithelial cells.
Conclusions. Here we present the TGF-β pseudoreceptor BMP and Activin
Membrane-Bound Inhibitor (Bambi) as a new modulator of TGF-β
signaling which might play a potent role in controlling the tissue homeostasis
and involvement in infection triggered pathogenesis.
FR-P-145
The contribution of p120-catenin modulated NF-kappa B activation
in airway inflammatory responses
X . Wang1 1Department of Pathology, Tongji Medical College Huazhong University of
Science and Technology, Wuhan, China
Aims. The purpose of this study is to investigate the role of p120-catenin
(p120) modulated nuclear factor-kappa B (NF-kappa B) activation
in airway inflammatory responses, and further to explore the molecular
mechanisms.
Methods. In this study, human bronchial epithelial cells (BECs) were
treated with LPS to establish an airway inflammation model in vitro.
Using confocal immunofluorescence imaging, Western blot, isolation of
cytoplasmic and nuclear proteins, we examined the localizations and expressions
of p120, NF-kappa B, IkappaB alpha and RhoA. Immumoprecipitation
was used to confirm the direct interaction of p120 and RhoA.
The RhoA activity was examined by G-LISA method. Then we detected
the expressions of interleukin-8 (IL-8) by fluorescence quantitative PCR
and enzyme-linked immunosorbent assay. Luciferase reporter analysis
was used to detect the activity of NF-kappa B. Finally, transient transfection
and small interfering RNA (siRNA) were used for p120 overexpression
or knock-down, and then the effects of p120 on NF-kappa B
signaling pathway were detected.
Results. In the present study, we first confirmed that p120 expression was
significantly reduced after LPS stimulation in BECs, the nuclear translocation
of NF-kappa B p65 subunit was promoted, IkappaB alpha was
phosphorylated and degraded, and NF-kappa B activity was rapidly induced.
After LPS stimulation, although the total RhoA and p120-binded
RhoA were unchanged, the RhoA activity is increased. Moreover, the
expression level of IL-8 increased after LPS treatment. Overexpression
of p120 attenuated LPS-stimulated NF-kappa B reporter gene expression
and IL-8 mRNA expression and protein synthesis. On the contrary,
transfection with p120 siRNA significantly elevated LPS-stimulated
NF-kappa B transcriptional activity, p65 nuclear translocation and IL-8
expression.
Conclusions. Collectively, these results indicate an anti-inflammatory effect
of p120 in BECs, through its modulation of NF-kappa B signaling in
a RhoA dependent manner.
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