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

Conclusions. To our knowledge, this case represents the first report of
solitary myofibroma presenting as a thyroid mass. Awareness of this differential
diagnosis is necessary to avoid misinterpretation as a sarcoma
with the sequelae of unnecessary over-treatment.
Poster: Uropathologie I
SA-P-078
Rearrangement of the ETS genes ETV-1, ETV-4, ETV-5 and ELK-1 is
a clonal event during prostate cancer progression
M . Braun1 , Z . Shaikhibrahim1 , P . Nikolov1 , D . Böhm1 , V . Scheble2 , R . Menon1 ,
F . Fend3 , G . Kristiansen1 , N . Wernert1 , S . Perner1 1 2 University Hospital Bonn, Institute of Pathology, Bonn, University Hospital
Tübingen, Division of Hematology and Oncology, Tübingen, 3University Hospital Tübingen, Institute of Pathology, Tübingen
Aims. ETS gene rearrangements are frequently found in prostate cancer
(PCa). Several studies have assessed the rearrangement status of the most
commonly found ETS gene, ERG, and the less frequent genes, ETV-1,
ETV-4, ETV-5 and ELK-4 in primary PCa. However, the frequency in
metastatic disease is still not well investigated. Recently, we have assessed
the ERG rearrangement status in both primary PCa and the corresponding
lymph node metastases, and observed that ERG rearrangement in
primary PCa transfers into lymph node metastases, suggesting it to be a
clonal expansion event during PCa progression. As a continuation, we
investigated in this study whether this observation is valid also for the
less frequent ETS rearranged genes ETV-1, ETV-4, ETV-5 and ELK-4.
Methods. Using dual color break-apart FISH assays, we evaluated the status
of all the less frequent ETS gene rearrangements for the first time on
tissue microarrays (TMAs) constructed from a large cohort comprised
of primary PCa and the corresponding lymph node metastases. Additionally,
we evaluated the rearrangement status of all these ETS genes in a
second cohort comprised of distant metastases.
Results. ETV-1, ETV-4, ETV-5 and ELK-4 rearrangements were found in
8/81 (10%), 5/85 (6%), 1/85 (1%) and 2/86 (2%) of the primary PCa, respectively,
and in 6/73 (8%), 5/85 (6%), 4/72 (6%), 1/75 (1%) of the corresponding
lymph node metastases, respectively. Rearrangements of ETV-1 and
ETV-5 were not found in any of the distant metastases cases, whereas
ETV-4 and ELK-4 rearrangements were found in 1/25 (4%) and 1/24 (4%)
of the distant metastases, respectively.
Conclusions. Our results suggest that rearrangement of the less frequent
ETS genes is a clonal event during prostate cancer progression. Our findings
provide insights into potential clonal expansion events during PCa
progression and may have significant implications in understanding the
molecular basis of the metastatic cascade of PCa.
SA-P-079
ERG protein expression and genomic rearrangement status in
primary and metastatic prostate cancer – a comparative study of
two monoclonal antibodies
M . Braun1 , D . Goltz1 , Z . Shaikhibrahim1 , W . Vogel 1 , D . Böhm1 , V . Scheble2 ,
K . Sotlar3 , F . Fend4 , A . Dobi5 , G . Kristiansen1 , N . Wernert1 , S . Perner1 1 2 University Hospital Bonn, Institute of Pathology, Bonn, University Hospital
Tübingen, Division of Hematology and Oncology, Tübingen, 3University Hospital Munich, Institute of Pathology, München, 4University Hospital
Tübingen, Institute of Pathology, Tübingen, 5Uniformed Services University
of the Health Sciences, Center for Prostate Disease Research, United States
Aims. Overexpression of the ERG protein is highly prevalent in prostate
cancer (PCa) and most commonly results from gene fusions involving
the ERG gene. Recently, an N-terminal epitope targeted mouse and a
C-terminal epitope targeted rabbit monoclonal anti-ERG antibody have
been introduced for the detection of the ERG protein. Independent studies
reported that immunohistochemical (IHC) stains with both monoclonal
anti-ERG antibodies (ERG-MAbs) highly correlate with the
underlying ERG gene rearrangement status. However, a comparative
study of both antibodies has not been provided so far. Here, we are the
first to compare the mouse ERG-MAb to the rabbit ERG-MAb for their
concordance on the same PCa cohort. Furthermore, we assessed if the
ERG protein expression is conserved in lymph node and distant PCa metastases,
of which a subset underwent decalcification.
Methods. We evaluated tissue microarrays of 278 specimens containing
265 localized PCa, 29 lymph node, 30 distant metastases, and 13 normal
prostatic tissues. We correlated the ERG protein expression with the
ERG rearrangement status using an ERG break-apart fluorescence insitu
hybridization (FISH) assay and IHC of both ERG antibodies.
Results. ERG protein expression and ERG rearrangement status were
highly concordant regardless of whether the mouse or rabbit ERG-MAb
was used (97.8% versus 98.6%, respectively). Of interest, both ERG antibodies
reliably detected the ERG expression in lymph node and distant
PCa metastases, of which a subset underwent decalcification. Lymphocytes
revealed immunoreactivity using the rabbit ERG-MAb, but not
using the mouse ERG-MAb. If an ERG protein expression was present
in localized PCa, we observed the same pattern in the corresponding
lymph node metastases.
Conclusions. This is the first study to comprehensively compare the two
available ERG-MAbs. By demonstrating a broad applicability of IHC to
study ERG protein expression using either antibody, this study adds an
important step towards a facilitated routine clinical application. Further,
we demonstrate that the clonal nature of the ERG rearrangement is not
restricted the genomic level, but proceeds in the proteome. Together, our
results simplify future efforts to further elucidate the biological role of
ERG in PCa.
SA-P-080
MicroRNA miR-205 is down-regulated in prostate cancer depending
on Gleason score and tumour size
B . Verdoodt1 , M . Vogt1 , V . Kuhn1 , A . Tannapfel1 , A . Mirmohammadsadegh 1 , M .
Neid1 1Ruhr-University Bochum, Institute for Pathology, Bochum
Aims. miR-205 plays a role in the repression of the epithelial to mesenchymal
transition in different epithelial tumours, and targets anti-apoptotic
and cell cycle regulating genes. We studied the expression of miR-
205 and its relation to clinical parameters in archival samples of prostate
cancer with different Gleason scores.
Methods. miRNA was isolated by micro-dissection from 84 formalin
fixed/paraffin embedded prostatectomy specimens with prostate cancer
of Gleason score 3+3 (n=12), 3+4 (n=32), 4+3 (n=30), and 4+4 (n=10),
and from corresponding benign prostate tissue. miR-205 levels were determined
by quantitative real time PCR in comparison to RNU6B (U6
small nuclear RNA 2) as reference gene. Data was correlated with Gleason
score, size, and extraprostatic tumour extension.
Results. Expression of miR-205 was lower in tumour tissue than in benign
tissue from the same patient in 76 of 84 cases (90.5%, median expression
18%). It decreased depending on Gleason score, with median
0.303 in tumours with Gleason score 3+4, median 0.150 in tumours with
Gleason score 4+3, and median 0.087 in tumours of Gleason score 4+4
(p