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

internet server. A network of internationally recognized gynecological
pathologists is connected to the server through a custom-designed software
platform. If necessary, immunohistochemistry is available through
a collaborating pathology lab.
Results. The new internet-based high throughput infrastructure has
been set up successfully. Five gynecopathologists from Austria, Switzerland
and Germany will provide specialized review of all cases scheduled
for inclusion in the AGO OVAR17 trial for all study centers of the AGO
study group. A centralized office plays a key role in the logistics of the
complex course of action in central pathology review.
Conclusions. Preliminary data suggest that the use of a new internet-based
infrastructure may allow for specialized case review prior to patient
randomization in the AGO OVAR17 trial. This approach might not only
help to avoid disregarding of clinicopathologic inclusion criteria but also
to further improve the quality of patient care through minimization of
overtreatment with chemotherapy of patients with ovarian borderline
tumors and inadequate treatment of patients with ovarian metastases.
SA-P-024
Metastatic sebaceous ovarian cancer
H . Geddert1 , A . Dimmler1 , M . Rauchholz2 , O . Tomé2 , G . Faller1 1 2 St . Vincent Hospital, Institute of Pathology, Karlsruhe, St . Vincent Hospital,
Department of Gynecology and Obstetrics, Karlsruhe
Aims. A 47-year-old patient complained of abdominal tenderness and
pain.
Methods. Ultrasound as well as thoracal, abdominal and pelvic computer
tomography demonstrated a heterogenic tumor of the left ovary measuring
14 cm. A singular lesion suspected of metastasis was identified as
well in the liver and the lung. A core biopsy from the pulmonary lesion
was collected preoperatively. Laparotomy with total abdominal hysterectomy,
bilateral salpingo-oophorectomy, infragastric omentectomy
and liver lesion biopsy was performed. During operation, no macroscopic
sign of peritoneal carcinosis was described.
Results. Histological examination of the ovarian tumor proved a sebaceous
carcinoma. No features of a teratoma were identified in the
completely sampled mass. Hepatic and pulmonary metastases were diagnosed
in the core biopsies. Unfortunately, the patient showed a rapid
progress postoperatively with increasing number and size of liver and
lung metastasis. Therefore, the patient was given chemotherapy with
Carboplatin and Paclitaxel.
Conclusions. To our best knowledge, this is the first reported case of a
sebaceous ovarian carcinoma with synchronous hepatic and lung metastasis.
SA-P-025
Histone-deacetylase-1 expression and intratumoral lymphocyte
density are prognostic parameters for predicting overall survival
in serous ovarian carcinoma
H . Bösmüller1 , J . Peper2 , B . Gückel3 , T . Fehm3 , C . Bachmann3 , D . Wallwiener3 , S .
Stefanovic2 , D . Pham4 , F . Fend4 , A . Staebler4 1Krankenhaus Barmherzige Schwestern, Dept . of Pathology, Linz, Austria,
2 3 University of Tübingen, Dept . of Immunology, Tübingen, University of
Tübingen, Dept . of Gynecology, Tübingen, 4University of Tübingen, Dept . of
Pathology, Tübingen
Aims. High level expression of histone deacetylases 1, 2 and 3 (HDAC) are
associated with progressive disease and poor prognosis in high-grade serous
ovarian carcinoma (SOC) and also are markers for potential treatment
with histone deacetylase inhibitors. Intratumoral lymphocyte density
is a parameter of antitumoral immunoreactivity and is associated
with prolonged overall survival. Since we recently identified HDAC1/2
by HLA ligandome analysis as HLA class I associated antigen in ovarian
cancer, we investigated HDAC 1 expression and T-cell density in a large
series of high-grade serous ovarian carcinomas.
Methods. Primary tumors of 141 patients with SOC in FIGO Stage II–IV
were studied by immunohistochemistry on tissue microarrays containing
6 cores per case. HDAC1 expression was assessed by applying the
semiquantative IRS score. The stromal and intraepithelial T-cell (CD3
and CD8) density was quantified, counting the average number of cells
per high power field (HPF=400x) and reviewing a total of 10 HPF for
each core.
Results. Strong nuclear HDAC1 expression (score 8, 9, 12) was associated
with poor overall survival (OS, median 25 vs. 40 months, p=0.008), but
not disease free survival (DFS median 23 vs. 27 months, p=0.378). Increased
intraepithelial CD3+ lymphocytes (p=0.012) and stromal CD8+ lymphocytes
(p=0.026) were associated with favourable OS, whereas DFS
was only significantly associated with stromal CD8 density (p=0.019).
Strong HDAC 1 expression correlated with increased cytotoxic lymphocyte
density (p=0.021, Pearson-correlation).
Conclusions. Our study of a large collective of advanced SOC confirms
the prognostic relevance of intratumoral lymphocyte density as well
as high HDAC1 expression. The observed correlation between HDAC1
overexpression and intraepithelial CD8+ T-cell density points to a
potential role of HDAC1 as a tumor specific antigen in SOC.
SA-P-026
Effects of MDM2 and MDMX splice variants on p53 pathway in
ovarian carcinomas
S . Hammer1 , S . Pelka1 , A . Wolf1 , A . Böhnke1 , S . Mahner2 , G . Ott3 , S . Hauptmann4
, F . Bartel1 1 2 University of Halle-Wittenberg, Institute of Pathology, Halle/Saale, University
Medical Center Hamburg-Eppendorf, Department of Gynecology,
Hamburg, 3Robert-Bosch-Hospital, Institute of Clinical Pathology, Stuttgart,
4Insitute of Pathology Allgäu-Oberschwaben, Wangen
Aims. Many human tumors show inactivation of p53 pathway e.g. due
to overexpression of the negative regulators MDM2 and MDMX. Both,
MDM2 and MDMX, are spliced alternatively and aberrantly in many tumor
cell lines. So far there are no studies about the expression and effects
of MDM2/X splice variants in ovarian carcinomas.
Methods. Therefore, we screened 33 frozen ovarian carcinoma samples
for the occurrence of MDM2/X splice variants. We detected beside the
known variants MDM2-B, MDMX-S and MDMX-211 new variants such
as MDM2-p53NLS, MDM2-ARZ, MDMX-A, MDMX-Z and MDMX-
ZR containing different domains. Subsequently, the ovarian tumor cell
lines OAW-42 and ES-2 were transfected with these variants and treated
with both cisplatin and taxol in order to analyze their effects on the p53
pathway after DNA damage.
Results. Overexpression of MDM2-p53 and MDM2-p53NLS resulted in
stabilization of p53 but not in induction of p21 expression. In contrast
MDM2-AZR and-B did not change p53 level but slightly increased p21
expression after cisplatin. Both MDMX-A and MDMX-211 stabilize
MDMX which caused a transcriptional inactivation of p53 after cisplatin
treatment.
Conclusions. Our results clearly show, that MDM2 and MDMX splice variants
affect p53 pathway which may had an impact on tumor formation
and/or chemoresistance.
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