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

on primary cells of wild-type and cathepsin X knockout epithelial cells
with infection by H. pylori were performed to confirm the descriptive
data on tissue samples.
Results. Galectin-2 is constitutively expressed in gastric mucosa of wildtype
and cathepsin-X knockout mice. Galectin-2 expression is decreased
in gastric inflammation and spasmolytic polypeptide-expressing metaplasia
(SPEM). H. pylori infection leads to lower mRNA- and protein-levels
of galectin-2 in wild-type and cathepsin-X knockout mice. However,
levels of galectin-2 were significantly higher in cathepsin-X knockout
mice compared to wild-type mice independent of H. pylori infection.
Infection of primary cells revealed comparable results.
Conclusions. Because galectin-2 expression is decreased in gastric inflammation
and cathepsin-X is increased we propose an inverse regulation
of these molecules in gastric inflammatory disease. Since there is an
intense and smooth expression of galectin-2 in healthy gastric mucosa,
treatment of patients with galectin-2 could help to prevent epithelial damage
and thus decelerate gastric carcinogenesis.
FR-P-049
Krukenberg tumor with partial yolk sac differentiation or collision
tumor? A case report
A . Weber1 , A . Schmieder1 , K .-H . Berghaeuser1 , T . Friedrich1 1Institut of Pathology, Saalfeld
Aims. A 28-year-old woman suffered from a diffuse infiltrating gastric
carcinoma. After chemotherapy with ECF, subtotal gastrectomy with
Roux-Y reconstruction was performed before.
Methods. In microscopic examination of the tumor diffuse carcinoma
without any other differentiation was diagnosed. Tumor regression was
estimated to 40% at time of surgery staging was ypT2b ypN0 cm1 (PER).
Despite of adjuvant chemotherapy six months later malignant ascites
and peritoneal dissemination of the tumor with the same differentiation
occurred. Two years later two metastases were removed from the
peritoneum with the same histological appearance. At that time both
enlarged ovaries were removed.
Results. Histologically, in both ovaries metastases of the diffuse carcinoma
were found. In addition in the left side was a definite area with large
clear cells according to yolk sac differentiation. Immunhistologically
this area with cells reacted positively with AFP and CK 7.
Conclusions. Adenocarcinomas of stomach with yolk sac differentiation
are extremely rare. It remains to be clarified if in this case there is one of
this rare adenocarcinomas or a collision tumor combining metastases of
signet ring cell carcinoma of the stomach with a primary yolk sac tumor
of the ovary.
FR-P-050
FoxO6 expression in gastric cancer
J . Haag1 , B . Ingold-Heppner2 , H .-M . Behrens1 , T . Aigner3 , C . Röcken1 1 2 Christian-Albrechts-University Kiel, Institute of Pathology, Kiel, Charité
Campus Mitte, Institute of Pathology, Berlin, 3Klinikum Coburg, Institute of
Pathology
Aims. The expression of the transcription factor FoxO6 in gastric cancer
and the correlation of FoxO6 expression levels to clinicopathological tumor
characteristics were evaluated.
Methods. Study population: 485 cases with cancer of the stomach or oesophagogastric
junction were characterized for type of surgery, age at
diagnosis, gender, tumor localization and tumor size, tumor type, tumor
grade, depth of invasion, number of lymph nodes resected, and number
of lymph nodes containing metastases. Tumors were classified according
to the Laurén classification and the mucin phenotype. pTNM-stage of all
study patients was determined according to the 7th edition of the UICC
guidelines and our recent proposal (“Kiel-stage”). Mismatch DNA repair
capacity and microsatellite instability was analyzed by immuno-
histochemistry and a pentaplex PCR assay. Analysis of FoxO6 expression:
polyclonal rabbit antisera were generated against human FoxO6. A
FoxO6 specific peptide (NH2-)CAQDAYGPRARAGTP(-CONH2) was
synthesized, coupled to a carrier molecule and injected into two rabbit
hosts. Antisera were obtained at day 84 of immunization and purified
by peptide affinity chromatography using a FoxO6 specific peptide affinity
column (Innovagen, Lund, Sweden). Tissue micro arrays (TMA)
were prepared to study the expression of FoxO6 in the study population.
FoxO6 immunostaining of the TMAs was evaluated by applying
an immunoreactivity scoring system [0 (no immunostaining), 1 (weak),
2 (moderate), and 3 (strong)]. Statistics: Statistical analyses were done
with SPSS 18.0. With respect to continuous variables, cases were divided
into two groups by splitting at the median value. Significance of correlation
between clinicopathological parameters and FoxO6 expression was
tested using Fisher’s exact test. For parameters with ordinal scale (T, N,
stage) we applied Kendall’s tau test instead. Generally, p-values less than
0.05 were considered statistically significant.
Results. FoxO6 staining was found exclusively in the cytoplasm, no nuclear
staining was detected. Expression levels were heterogeneous when
different cases were compared. Statistically significant correlation to the
FoxO6 expression levels were found for the Lauren phenotype, the Tcategory,
the mucin phenotype and the microsatellite instability status.
Conclusions. The correlation of FoxO6 expression levels with major clinicopathological
tumor characteristics warrants further analysis of the
biological role of FoxO6 in gastric cancer.
FR-P-051
Differential expression of LGR4, LGR6, GPR34, GPR160 and
GPR171 in gastric carcinoma
J .S . Steffen1 , E . Simon1 , K . Balschun1 , C . Böger1 , C . Röcken1 1Christian-Albrechts-University, Institute of Pathology, Kiel
Aims. Gastric cancer (GC) is one of the most common causes of cancerrelated
deaths worldwide. Due to its poor prognosis, the identification of
novel therapeutic targets is of high priority. G-protein-coupled receptors
(GPCRs) are prime candidates for novel cancer prevention and treatment-strategies,
since they play an important role in regulating physiological
and pathophysiological processes. These receptors form the largest
family of human membrane-bound proteins and represent a target
for more than 40% of all drugs. We aimed to elucidate the differential
expression and putative tumor biological significance of LGR4, LGR6,
GPR34, GPR160 and GPR171, in GC.
Methods. Based on our previous microarray analysis we identified five
candidate genes in human gastric cancer samples. Real time RT-PCR
was carried out to validate their expression in malignant and non-malignant
tissue on an independent collective comprising 32 GC patients with
and without lymph node metastases. Selected protein targets LGR4 and
LGR6 were further validated on paraffin-embedded sections of 10 intestinal
and 10 diffuse type gastric carcinomas and their corresponding
non-malignant tissue using immunohistochemistry. Additionally, the
putative tumour biological significance of LGR4 and LGR6 was studied
using tissue micro arrays obtained from a cohort of 488 GCs.
Results. GPR34, GPR160 and GPR171 did not show any differential expression
in real-time RT-PCR analyses. LGR4 and LGR6 were markedly
up-regulated on transcriptional (real-time RT-PCR) and translational
(immunohistochemistry) level in GC. Furthermore, in tissue micro
array analysis LGR6 expression was significantly associated with local
tumor growth (T-category) and correlated with patient survival. LGR4
expression was significantly correlated with the lymph node metastases
(N-category).
Conclusions. LGR6 has recently been identified as stem-cell marker in
the skin whereas LGR4 is of known tumor biological relevance in colon
carcinoma and other malignancies. Our systematic analysis indicates
that these two genes also play a role in gastric cancer biology. Future stu-
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