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

Abstracts
Results. Test positivity rates for dual-stained cytology, Pap, and HPV
testing over all ages were 5.7%, 5.6%, and 11.2%, respectively. Sensitivity
of dual-stained cytology for CIN2+ (n=67 cases) was found at 95.6%
(95% CI 87.1–98.6%), significantly higher than Pap cytology (80.2%;
95% CI 68.5–88.3%). Specificity levels were identical for both methods
(95.0% for dual-stained cytology vs. 95.1% for Pap testing). In women
aged 30 and older, sensitivity (specificity) of dual-stained cytology for
CIN2+ was 91.2% (96.0%), compared to 77.9% (95.9%) for Pap testing and
96.1% (92.1%) for HPV testing. For the triage of abnormal Pap cytology
results, dual-stained cytology showed identical (ASC-US triage: 100%
for both tests) or similar (LSIL triage: 94.5 vs. 100%) sensitivity as HPV
testing for the detection of underlying CIN2+, at significantly higher specificity
rates.
Conclusions. p16/Ki-67 dual-stained cytology performed on ThinPrep®
liquid-based cytology may achieve a sensitivity level as high as 95% for
underlying CIN2+ in primary screening of women of all ages, combined
with a 95% specificity. Furthermore, dual-stained cytology was shown to
be a highly efficient tool for the triage of abnormal Pap cytology results
when performed as a reflex test out of ThinPrep liquid-based cytology
specimens.
SO-020
Frequency of BRAF-p.V600E mutation in serous ovarian borderline
tumors and its peritoneal implants
A .K . Höhn1 , U . Siebolts1 , J . Einenkel2 , L .-C . Horn1 1 2 University of Leipzig, Institute of Pathology, Leipzig, University of Leipzig,
Department of Obstetrics and Gynecology (Institute of Trier), Leipzig
Aims. Genes of the RAF family, which mediate cellular responses to
growth signals, encode kinases that are regulated by RAS and participate
in the RAS/RAF/MEK/ERK/MAP-kinase pathway. Activating mutations
in BRAF have been identified to play a major role in the pathogenesis
of low-grade serous ovarian carcinomas (LG-OCA) via serous borderline
tumors (s-BLT; Sieben et al. 2004, Mayr et al. 2006; Vang et al. 2009).
But, limited information exists about a possible clonal relation comparing
s-BLT and its peritoneal implants which we want to illuminate by
BRAF p.V600E analysis.
Methods. Thirteen cases of s-BLT with peritoneal implants (invasive and
non-invasive) were identified from our files with subsequent macro- or
microdissection followed by DNA extraction of the adequate tissue. To
reveal the activating mutation of BRAF p.V600E we performed pyrosequencing
of 48 samples with a sensitivity of at least 5% mutated alleles.
Molecular analysis was performed from the ovarian tumor as well as
within one to 6 peritoneal implants from different sites.
Results. Five s-BLT (38.5%) showed BRAF-p.V600E mutation within the
ovarian tumor. In three of those cases BRAF-p.V600E mutation was also
identified within the peritoneal implants suggesting a clonal origin in
terms of abdominal tumor spread.
Conclusions. The frequency of BRAF-p.V600E mutation in s-BLT is concordant
with the reported frequency within LG-OCA. In case of abdominal
spread, peritoneal implants represent clonal origin of the primary
tumor in about two thirds of the informative cases. Further studies, examining
additional members of the RAS/RAF/MEK/ERK/MAP-kinase
pathway and using laser-capture microdissection in cases of rare tumor
epithelium by atrophy are required.
66 | Der Pathologe · Supplement 1 · 2012
SO-021
The relevance of steroid hormone receptors (estrogene alpha and
beta, progesterone), luteinizing hormone and follicle-stimulation
hormone receptor as well as aromatase activity in granulosa cell
tumors (GCTs) of the ovary
M .C . Jarrin Franco1 , T . Kirchner1 , J . Engel2 , S . Lauf3 , A . Mayerhofer4 , D . Mayr1 1 2 University of Munich, Institute of Pathology, München, University of
Munich, Munich Tumor Registry, München, 3University of Munich, Institute
of Cell biology, München, 4University of Munich, Institute of Anatomy,
München
Aims. Granulosa cell tumors of the ovary (GCTs) are rare neoplasms
from sex-cord stromal cells with a general trend toward late relapse and
metastasis. In contrast to ovarian carcinomas, tumor stage is the only
prognostic factor. The pathophysiology of ovarian tumors and relationship
to hormonal control are not yet fully understood, but the ovary is
the principal source of estrogens and one of their target organs. Some
aromatase inhibitors are relatively well-tolerated oral drugs commonly
used in breast cancer treatment. The aim of this study was to investigate
the tumorigenesis of GCTs, regarding steroid hormone receptors, luteinizing
hormone and follicle-stimulation hormone receptor and aromatase
activity with correlation to clinical data and survival.
Methods. 43 cases of GC-tumors of 36 patients from the archive of the
Department of Pathology, LMU Munich were selected. Immunohistochemical
assays (IHC) and RT-PCR were performed by standard methods.
The IHC for ER alpha, ER beta and progesterone was evaluated
by using the IRS-score. For aromatase activity, FSH and LH a 4-tired
scoring system was developed. The results were correlated to each other
and to clinical data (e. m. TNM-stage, Ki-67 proliferation index, progression)
and survival.
Results. Positive results for IHC: ER alpha in 79.1%, ER beta in 86%, PR
in 97.7%, FSHR in 14%, LHR in 25.6% and aromatase in 51.2%. Positive results
for RT-PCR: ER alpha in 88.4%, ER beta in 100%, PR in 86%, FSHR
in 55.8%, LHR in 76.7% and aromatase in 74.4%. No statistical correlation
between IHC and RT-PCR could be demonstrated. A significant correlation
between T-stage and IHC for ER alpha (p=0.026), ER beta (p=0.01),
progesterone (p=0.042) and Ki67 (p=0.046) was observed. Only for ER
beta-IHC a high statistical significance (p=0.019) in correlation to progression
could be demonstrated. No statistical significance between Tstage
and RT-PCR results could be demonstrated in any case. Regarding
the progression and survival, the only statistical significance could be
demonstrated for RT-PCR of LHR (p=0.030).
Conclusions. At the present time tumor stage and in some studies Ki-67
proliferation are the only established prognostic factors for GCTs. A long
follow-up is the only way of validation the success of treatment. Regarding
our results, ER beta and RT-PCR of LHR could be new prognostic
signs and beyond that a basis for a new therapeutic strategy. Analyses of
a larger number of cases, as well as studies of cell culture are already in
progress.