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

in the context of therapy response before. Immunohistochemistry of
the mitochondrial protein COX7A2 in the validation set confirmed the
MALDI Imaging results and revealed the predictive impact of COX7A2
(p=0.0015). By electron microscopy we found, that the loss of these proteins
is strongly associated with a severe mitochondrial damage.
Conclusions. MALDI Imaging is able to detect novel proteomic patterns
distinguishing responders from non-responders. These protein patterns
provide new insights in mechanisms of response. For the first time we
could show that mitochondrial dysfunction is a predisposition for response
to neoadjuvant chemotherapy in Barrett’s cancer.
FR-P-043
Heterogeneity of TP53 mutations in gastric adenocarcinomas as
well as their corresponding lymph node metastases
D . Mones1 , G . Cadeddu1 , K .-L . Schäfer1 , H .E . Gabbert1 , S .E . Baldus1 1University of Düsseldorf, Institute of Pathology, Düsseldorf
Aims. The frequency of TP53 mutations in gastric adenocarcinomas as
well as the prognostic and predictive value of this biomarker is still controversially
discussed. In order to elucidate if genetic mosaicism may
explain at least in part the conflicting results obtained in previous studies,
we investigated the intratumoral heterogeneity of TP53 mutations
analysing tissue specimens from tumor center, invasion front and lymphonodal
metastases.
Methods. We studied a series of 75 gastric adenocarcinomas comprising
25 diffuse type, 24 intestinal type and 26 mixed type carcinomas according
to Laurén. DNA of the paraffin-embedded tissue samples from tumor
center and invasion front (n=75) as well as corresponding lymph
node metastases (n=47) was obtained by microscopically controlled manual
microdissection. DNA was purified and subjected to PCR amplification
of TP53 exon 5–8 followed by direct sequencing.
Results. TP53 mutations were observed in 34 of the 75 primary tumors
(45%). Intratumoral heterogeneity of TP53 mutations was found in 13
primary tumors (17%): Two samples showed the mutation only in the
invasion front, ten cases only in the tumor center and one case showed
different mutations in invasion front and tumor center. There was no
significant difference between the mutation rates in diffuse type (40%)
compared to intestinal type adenocarcinomas (50%), while mixed type
carcinomas showed a mutation in 46% of the cases. In addition, there
was no difference between pT1/pT2 tumors (46%) and pT3/pT4 tumors
(45%). Mutations in the lymph node metastases were found in 19 of 47
specimens (40%). Genetic heterogeneity between primary tumor and
lymph node metastases was observed in 12 of the 47 cases (26%) comprising
six cases showing the TP53 mutation only in the primary tumor,
but not in the lymph node metastasis as well as four cases exhibiting a
mutation in the lymph node metastasis, but not in the primary tumor.
In two cases different mutations in primary tumor and corresponding
lymph node metastasis were observed.
Conclusions. Intratumoral heterogeneity of TP53 mutations is present in
17% of gastric adenocarcinomas and may therefore contribute to the controversial
results regarding the prognostic value of the TP53 status. In
addition, in 26% of the cases heterogeneity between TP53 mutations in
primary tumors and lymph node metastases was observed. This should
be considered in future studies on the predictive and prognostic value of
TP53 mutation analysis in gastric adenocarcinomas.
FR-P-044
Gastric Polyvinylpyrrolidon (PVP) Athrozytosis in chronic hemodialysed
patients
S .A . Thies1 , B . Kaduk2 , R . Ott3 , S . Turi4 , M . Sarbia5 1University of Zurich, Institute of Surgical Pathology, Zürich, Switzerland,
2 3 Kaduk Medical Service (KMS) GmbH, Baar, Switzerland, Gastroenterologie
Bogenhausen, Gemeinschaftspraxis Dr . Schatke, Munich, 4Medizentrum Erlangen, Gemeinschaftspraxis Internist/Gastroenterologie, Erlangen,
5Pathologie München Nord, Munich
Aims. The originally as plasma expander developed and applied high
molecular Polyvinylpyrrolidone (PVP) – a polymer of the monomer
N-Vinylpyrrolidon cannot be eliminated by diuresis nor metabolised
by liver. These PVP polymers were phagocytosed by macrophages and
permanently arrested. According to the type and topos of application of
PVP – intradermal, subcutaneous, intracavitary, intraperitoneal, interpleural
or intravenous – the phenotype of this storage disease differs and
is predictive. The only non-predictive manifestation and severity of the
accumulation and conditio sine qua non is due to the entrance of the
high molecular PVP polymers into the blood circulation. This induces a
high risk situation for the patients. For that reason high molecular PVP
is not yet used as plasma expander. But nevertheless there is an ubiquitary
(generalised) PVP-thesaurismosis, e.g. using PVP-coating fibre filters
in human hemodialysis.
Methods. We examined gastric biopsies of two patients with chronic hemodialysis
in history without defined clinical question. The main histological
topic was aggregates of isolated or grouped large macrophages
with a certain but non-characteristic staining pattern (indirect indicators
for PVP; i.e. advice):
– H&E: intracytoplasmic blue-gray globules
– Sirius red: brightly red deposits on a pale yellow background
– Argentic impregnation: markedly coloured dark black deposits
– PAS: negative
– v. Kossa: negative
– Immunocytochemically: CD68+++
Results. The definitive morphological typing of the macrophages as high
molecular PVP-containing macrophages could only approved by the
investigation of the ultrastructure in transmission electron microscopy
(direct indicator for PVP; i.e. evidence): intracytoplasmic globules of different
size and periodic lamellate internal structure.
Conclusions. The results of this study are essential for the manufacture
of dialyse membranes by advancement the adhesion of PVP and for the
patients to prohibit the generalized PVP-thesaurismosis. Also the findings
are helpful for the clinicians, notably for nephrologists in the surveillance
of chronic hemodialysed patients, for gastroenterologists and
for pathologists to receive an algorithm of the diagnostic relevant panel.
FR-P-045
Interaction of cathepsin X with galectin-2 in H. pylori dependent
gastric carcinogenesis
A . Teller1 , D . Kuester1 , A . Roessner1 , S . Krueger1 1Otto-v .-Guericke University, Department of Pathology, Magdeburg
Aims. Our previous studies have shown an association between Helicobacter
pylori infection, the strong up-regulation of cathepsin X (CTSX),
and the development of gastric cancer. The physiological function of
CTSX still needs to be clarified. In a yeast two-hybrid screen we could
identify galectin-2 as a novel interaction partner of cathepsin X. Now we
suppose an interactive role of CTSX and galectin-2 in modulation of the
immune system in response to H. pylori-infected gastric epithelial cells.
Methods. Background for further experiments was the screening of the
yeast two-hybrid system, where we could identify galectin-2 as a novel
interaction partner of CTSX. Using Western blots and immunohistochemistry
we want to analyze galectin-2 levels in biopsy specimens of
H. pylori-infected and non-infected patients as well as in gastric cancer
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