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

Abstracts
SA-P-021
The G-protein coupled estrogen receptor 1 (GPER) is differentially
expressed in healthy human ovaries, accompanies progression
into non malignant ovarian diseases, and predicts prognosis in
ovarian cancer patients
S . Heublein 1 , M . Lenhard 2 , J . Schöpfer 3 , C . Kuhn 1 , K . Friese 1 , A . Makrigiannakis
4 , U . Jeschke 1 , D . Mayr 5
1 Ludwig-Maximilians-University of Munich – Campus Innenstadt, Department
of Gynecology and Obstetrics, Munich, 2 Ludwig-Maximilians-University
of Munich, Department of Gynecology and Obstetrics – Campus Grosshadern,
Munich, 3 Ludwig-Maximilians-University of Munich, Department of
Legal Medicine, Munich, 4 University of Crete, Department of Obstetrics and
Gynaecology, Heraklion, Greece, 5 Ludwig-Maximilians-University of Munich,
Department of Pathology, Munich
Aims. In the ovary deregulation of estrogen signalling is tightly linked
to impaired fertility as well as to benign and malignant ovarian diseases.
However several of these estrogen mediated effects are clearly independent
of the classical DNA binding estrogen receptors. Thus to understand
which role the G-protein coupled estrogen receptor 1 (GPER)
plays within these processes might define implications for estrogen or
anti-estrogen based therapies. Therefore we examined GPER in healthy
human ovaries, human folliculogenesis, benign ovarian diseases as well
as in epithelial ovarian cancer (EOC) specimens in a large patient cohort
(n=282).
Methods. Immunohistochemistry, double immune fluorescence and
TaqMan® real time PCR were employed to determine GPER expression.
Ovaries of 32 pre- and 10 postmenopausal women were compared to
84 women affected by follicle cysts (n=14), serous (n=16) and mucinous
(n=18) cystadenofibroma, endometriosis (n=26) or reactive inflammatory
diseases (n=10). We further evaluated how GPER correlates with grading,
FIGO stage and prognosis in 156 EOC patients. Finally different
ovarian cell lines were used to test these interactions functionally.
Results. In healthy follicles GPER is abundantly present in oocytes and
theca cells followed by granulosa cells. In contrast to controls a pronounced
stroma expression of GPER was observed in endometriosis and inflamed
tissue which stresses its immune responsiveness to glucocorticoids
and galectin found in vitro. GPER is highly expressed in the ovarian
outer surface epithelium and down regulated in some entities of benign
neoplasias. In EOC low tumour grade and advanced prognosis were
predicted by elevated GPER. Furthermore here GPER showed positive
correlation to gonadotropine receptors, Galectin-3 and downregulation
of p53.
Conclusions. GPER is detectable in highly specialized cells throughout
human folliculogenesis and thus might be functionally involved in follicle
maturation. Progression into benign and malignant ovarian diseases
is accompanied by GPER, which we found is regulated by immune modulators
in different cell lines. Thus we conclude that GPER is a valuable
tool to further investigate human ovarian (patho-)physiology and that it
might be interesting for therapeutic interventions in EOC patients.
146 | Der Pathologe · Supplement 1 · 2012
SA-P-022
PDGF-C expression in ovarian cancer
A .-K . Zimmermann1 , A . Noske1 , H . Li2 , U . Ericsson2 , A .M . Neville3 , R . Caduff1 , H .
Moch1 , D . Fink4 , G . Kristiansen5 1University Hospital Zurich, Department of Surgical Pathology, Zürich,
Switzerland, 2Ludwig Institute for Cancer Research, Stockholm Branch,
Sweden, 3Ludwig Institute for Cancer Research, University of Oxford Branch,
United Kingdom, 4University Hospital Zurich, Department of Obstetrics
and Gynecology, Zürich, Switzerland, 5University Hospital Bonn, Institute of
Surgical Pathology
Aims. Platelet-derived growth factors (PDGF) and its receptors (PDGFR)
promote tumor growth and angiogenesis and are therefore interesting
targets for anticancer therapies. So far, little is known about the expression
and prognostic role of PDGF-C in ovarian cancer.
Methods. We investigated a cohort of 131 invasive ovarian carcinomas
and 31 borderline tumors for PDGF-C expression by immunohistochemistry
(using a specific antibody against this ligand) and compared expression
data with clinicopathological findings and patient overall survival.
Results. We observed an epithelial and stromal expression of PDGF-C
in 64 (49%) and 62 (48%), respectively of the ovarian carcinomas but did
not find any association with clinicopathological features or overall survival.
In a subgroup analysis of serous carcinomas, we observed a trend
of high PDGF-C levels with higher tumor grade (p=0.047). An epithelial
and stromal expression was also observed in borderline tumors in 65%
(22/34) and 26% (8/31), respectively.
Conclusions. This study shows that PDGF-C is overexpressed in a subset
of ovarian carcinomas but not associated with traditional prognostic
pathological factors or patient survival. However, PDGF-C has potential
as a therapeutic target and in context with the literature it might have a
predictive function in anti-VEGF-treatment.
SA-P-023
AGO VISION-1: Improved utilisation of resources and optimization
of quality of care through internet-based second opinion pathology
– standardized in an optimized ovarian cancer network
S . Kommoss1 , J . Pfisterer2 , J . Diebold3 , S . Lax4 , D . Schmidt5 , A . Staebler6 ,
A . du Bois7 , F . Kommoss5 1University of British Columbia, Department of Pathology, Vancouver,
Canada, 2Klinikum Solingen, Dept of Gynecology, Solingen, 3Luzerner Kantonsspital, Institute of Pathology, Luzern, Switzerland, 4LKH Graz West,
Institute of Pathology, Graz, Austria, 5Institute of Pathology, A2 , 2 , Mannheim,
6 7 University of Tübingen, Institute of Pathology, Tübingen, Kliniken Essen
Mitte (KEM), Dept Gynecology & Gyn . Oncology
Aims. Based on the literature as well as on own results from a prospective
study one may assume that a considerable number of patients in clinical
trials of ovarian carcinoma have diagnoses in conflict with inclusion
criteria. Subsequently clinical trials may be biased through unintended
disregarding of histological inclusion criteria. To avoid the latter limitation,
specialized pathology review should become standard procedure
in study protocols prior to randomization. To facilitate specialized second
opinion pathology prior to randomization and/or treatment decisions
the process of pathological case review has to be completed within
a few working days. We hypothesize that our new, internet-based high
throughput infrastructure will be capable of providing specialized second
opinion pathology within 10 working days.
Methods. Patients scheduled for the AGO OVAR17 trial have to be registered
for a central pathology review, which has to be performed through
the translational subproject termed “AGO VISION-1”. Having provided
written informed consent, the patients will be registered for pathology
review at a central office. Original slides will then be requested from the
outside pathologists in order to be scanned and uploaded to a secured