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

Abstracts
dies will have to demonstrate, whether these are also putative diagnostic,
prognostic and/or therapeutic targets for GC.
FR-P-052
Differential expression and abnormal cytoplasmic distribution of
E-cadherin and the desmosomal cadherin desmoglein 2 in gastric
carcinomas: Prognostic relevance of desmoglein 2-plaques
E .C . Scharbatke1 , A . Gamboa-Dominguez2 , F . Fend3 , A . Brunner4 ,
A . Schmidt1 , R . Moll1 1 2 Philipps University of Marburg, Institute of Pathology, Marburg, Instituto
Nacional de Sciencias Medicas y Nutricion Salvador Zubiran, Institute of
Pathology, Mexico City, Mexico, 3University Hospital Tübingen, Institute
of Pathology, Tübingen, 4University of Würzburg, Lehrstuhl für Volkswirtschaftslehre,
insbesondere Wirtschaftsordnung und Sozialpolitik, Würzburg
Aims. In gastric carcinomas, expression of E-cadherin has been shown
to be important in pathogenetic and prognostic terms. We compared expression
and subcellular distribution of E-cadherin and of another cellcell
adhesion molecule of the cadherin family, the desmosomal cadherin
desmoglein 2 (Dsg2), in a series of gastric adenocarcinomas of Mexican
patients.
Methods. Specimens of 63 cases of sporadic gastric adenocarcinomas
(26 of intestinal type, 37 of diffuse type; three cases showing CHD1
mutations) were analyzed immunohistochemically for E-cadherin and
Dsg2, using monoclonal antibodies AEC (clone 36; BD Transduction
Laboratories) and G129 (Progen, Heidelberg), respectively, on paraffin
sections after heat-induced antigen retrieval. Expression and subcellular
distribution (membrane staining, intracytoplasmic plaques ≤5 µm and
>5 µM) of these proteins were statistically correlated with clinicopathological
parameters and patient survival.
Results. 53 cases (84%) were positive for E-cadherin [19 cases (30%) with
plaques] and 62 cases (98%) were positive for Dsg2 [54 cases (84%) with
plaques]. Large intracytoplasmic plaques (>5 µM) were found for E-cadherin
in 5 cases (8%) and for Dsg2 in 9 cases (14%; three of intestinal and
six of diffuse type). The presence of E-cadherin or Dsg2 plaques of any
size and of large E-cadherin plaques did not show prognostic relevance.
However, the 9 patients with large Dsg2 plaques exhibited significantly
shorter survival (p=0.020) in multivariate regression analysis. This correlation
was independent from other parameters such as tumor stage.
Conclusions. Both cadherins studied are expressed differentially in gastric
carcinomas. Abnormal subcellular distribution of Dsg2 in the form of
large intracytoplasmatic plaques appears to be an independent predictor
of poor prognosis in gastric carcinomas. Prospective studies on larger
cohorts are required to confirm these results.
FR-P-053
Unexpected role of caspases in the survival of human colon epithelial
cells upon oxidative stress
A . Just1 , K . Reissig1 , R . Hartig2 , P . Steinberg3 , T . Guenther1 , A . Roessner1 ,
A . Poehlmann1 1Otto-von-Guericke University Magdeburg, Department of Pathology,
Magdeburg, 2Otto-von-Guericke University Magdeburg, Department of Molecular
and Clinical Immunology, Magdeburg, 3Institute of Food Toxicology
and Analytical Chemistry, Hannover
Aims. Current evidence suggests an increasing role for inflammation-associated
oxidative stress in colorectal cancer initiation. We found that
human colon epithelial cells (HCEC) survive oxidative stress through
cell cycle arrest. Moreover, caspases were found not to be involved in
apoptosis but in mediating the survival of HCEC. Thus, we aimed to unravel
their unexpected role.
Methods. We simulated acute inflammation by treating HCEC with a
pathophysiologic concentration of H2O2. We performed inhibition stu-
100 | Der Pathologe · Supplement 1 · 2012
dies using a pan-caspase inhibitor. The cells were further analyzed by
immunoblotting and FACS.
Results. H2O2 induces DNA damage in HCEC. As a consequence, HCEC
underwent apoptosis or cell cycle arrest to repair DNA damage. In addition,
a proportion of cells may progress through the cell cycle irrespective
of DNA damage (cellular survival). Surprisingly, caspase 3, 8 and 9
expression was found to be up-regulated, but did not precede cells into
apoptosis. To unravel the role of caspases in cell survival, we performed
inhibition studies using a pan-caspase inhibitor. Immunoblotting showed
(i) p21 and (ii) y-H2AX up-regulation following caspase inhibition.
Cell cycle analysis revealed the accumulation of cells in the G1 phase of
the cell cycle as the first response and increased apoptosis following caspase
inhibition as the second response. Because of these findings, we
suggest caspase-mediated inactivation of the tumor suppressor p21 and
the DNA damage sensor y-H2AX. Among others, this led us to suggest
that caspases rather play a role in survival than in apoptosis.
Conclusions. HCEC provide a model to analyze the molecular relationship
between inflammation-associated oxidative stress and colorectal
cancer initiation by mimicking the in vivo conditions in vitro. We suppose
that caspases promote cell survival upon acute colonic inflammation
through inactivation of p21 and y-H2AX. We presume (i) increased
proliferation due to p21 down-regulation and (ii) accumulation of DNA
damage because of y-H2AX down-regulation. Consequently, caspases
seem to mediate the progression of cells through the cell cycle irrespective
of DNA damage, and this might cause the cell to turn on a one way
street to malignant transformation.
FR-P-054
Uncommon coincidence of B-cell chronic lymphatic leukemia with
rare transversal-colon intussusception on older age flanked by a
simultaneous carcinoma of the right and left flexure – successful
management (only slight complication) with curative intent
M . Petersen1 , R . Kube2 , S . Dalicho1 , D . Wolleschak3 , H . Lippert1 , A . Roessner4 ,
F . Meyer1 1 2 University Hospital, Dept . of Surgery, Magdeburg, Municipal Hospital,
Dept . of Surgery, Cottbus, 3University Hospital, Dept . Hematology & Oncology,
Magdeburg, 4University Hospital, Institute of Pathology, Magdeburg
Aims. By means of an extraordinary case report, the rare hematological
case with a chronic lymphatic leucemia (CLL) and an associated malignoma
of the GI tract with the patient-related clinical finding and treatment
characteristics incl. “outcome” out of the daily clinical practice
with currently intermediary, interdisciplinary therapeutic success is
described.
Methods. Patient and diagnostic finding: approximately 4 weeks after
puncture of the bone marrow resulting in the diagnosis B-cell leukemia
(stage IIa according to the classification by BINET and RAI; initially:
Leucocytosis, hypochromic microcytic anemia), the patient (accompanying
diseases: Coronary heart disease, former acute myocardial infarction,
arterial hypertension, erosive gastritis) underwent surgical intervention
because of a simultaneously diagnosed double carcinoma of the
colon. Endoscopy revealed carcinoma (confirmed by histopathological
investigation of a specimen) of the descending colon and a suspicious
lesion of the ascending colon. CT scan excluded distal metastases and
described an intussusception of the transversal colon, infiltrationg tumor
growth through the whole colonic wall (1) and thickening of the
wall of the right colonic flexure (2).
Results. Treatment and course: intraoperatively, simultaneous double
colonic carcinoma of the right flexure and aborally of the left flexure
(no detection of an intussusception) was found prompting to a subtotal
colectomy with a 2-row ileosigmoideostomy to reconstruct intestinal
tract (1: pT2G2; 2: pT3N1[1/71]M0L0V0G2). There was only a summative
anemia through the postoperative course and following need of blood
transfusion. According to the oncological overall concept, an adjuvant