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

DNA damage, and cytotoxic drugs. Autophagy dysregulation is associated
with a number of disease states, including cancer. Autophagy plays
different roles during the initiation and progression of cancer. While
autophagy acts as a tumor suppressor during the initiation phase of cancer,
it promotes tumor progression and metastasis in established cancers.
Metastatic cancer cells that usually grow in a nutrient-poor microenvironment
utilize autophagy to fulfil their high metabolic demand. Autophagy
can facilitate survival during anchorage-independent growth
or anoikis, and promotes therapeutic resistance. Furthermore, recent
studies indicated that genetic or pharmacologic inhibition of autophagy
sensitized tumor cells to anti-cancer treatment. It is therefore important
to study the role of autophagy and its regulations in cancer cells, which
will help defining optimal strategies to modulate autophagy for therapeutic
advantage.
VO-038
Markers of autophagy in cancer
M . Muders1 1University Hospital Carl Gustav Carus at the University of Dresden,
Institute of Pathology, Dresden
Autophagy has been implicated in cancer progression and therapy resistance.
Accordingly, different methods to identify and quantify autophagy
in tissue samples and cell culture models will be applied more frequently.
The traditional way to visualize autophagy at the ultrastructural
level is electron microscopy. Electron microscopy has the ability to detect
important structures that are involved during lysosomal degradation of
organelles like autophagosomes. Easier and more cost effective is the immunohistochemical
detection of autophagy substrates like LC3 or p62.
In addition, proteins involved in autophagy like Beclin-1 could serve as
an indicator of autophagy. In cell culture models, functional studies like
detection of autophagic flux as well as long-lived protein degredation are
used to monitor autophagic activity. However, all methods have their limitations
and should be applied only after careful consideration of their
strengths and weaknesses.
Translationale Forschung und Diagnostik –
Mamma/Schilddrüse/Melanom
VO-039
Translationale Forschung und Diagnostik: Karzinome der Schilddrüse
A . Perren1 , A .M . Schmitt 1 , M . Dettmer2 1 2 Institut für Pathologie, Bern, Switzerland, University of Pittsburgh, Department
of Pathology and Laboratory Medicine, Pittsburgh, United States
Histopathology and treatment of thyroid carcinomas poses several challenges:
On a diagnostic level there is a group of tumors difficult (or impossible)
to classify as benign or malignant, more importantly, the 10%
of patients that cannot be cured by surgery and radio-iodine treatment
is difficult to predict. The grey zone of follicular thyroid tumors of unknown
malignant potential and morphological criteria of an adverse
outcome (poorly differentiated thyroid carcinomas and tall-cell papillary
thyroid carcinomas) will be discussed.
On a molecular level, well differentiated thyroid carcinomas are well
classified and the genetic basis is well known, however genetic events
during carcinoma progression are less well understood. The most important
genetic changes helping diagnosis, determination of prognosis
will be discussed. Their role in guiding future targeted therapy will have
to be shown in clinical trials.
VO-040
Translational research and diagnostics: Melanoma
J . Rüschoff and Panel Members of DGP/BDP BRAF Testing Ring Study 1
1Pathologie Nordhessen
Most recently the first molecularly defined targeted therapy in metastatic
and/or irresectable melanoma has been approved by EMA (20.2.2012).
Vemurafinib (Zelburaf) is a small molecule that selectively inhibits BRAF
kinase in its mutated form. About 50% of metastatic melanoma exhibit
mutations within the BRAF oncogene almost exclusively at codon V600
activating the RAS-RAF-MEK-ERK signal transduction pathway. About
90% of mutations lead to an exchange of valin and glutamate (V600E).
Within a large phase III clinical trial (BRIM3) median survival of Vemurafinib
treated patients was 5.3 months instead of 1.6 months after chemotherapy
with response rates of 48.4% versus 5.5%, respectively (Chapman
PB et al. NEJM 2011; Sosman JA et al. NEJM 2012).
In light of these data mutation testing of BRAF is becoming standard
of care in malignant melanoma. This raises the question about testing
methods and quality assurance. A working group of the DGP and BDP
has addressed these aspects by performing a ring study where 9 Institutes
of Pathology together with their clinical colleagues participated.
Recommendations of testing and evaluation have been determined and
a QUIP-based approach of quality assurance will be available in 04/2012
headed by the Universities of Heidelberg and Berlin [1]. Sensitivity and
specificity of testing platforms (Sanger-, Pyro-, 454-Sequencing, real-time-PCR-based
cobas® 4800) will be discussed together with the need of
a strict tissue based approach making use of tumor cell enrichment, e.g.
by microdissection.
In addition to BRAF testing in melanomas further mutation analyses
will be needed, e.g. of NRAS and CKIT, where targeted drugs are either
available (CKIT) or under development (NRAS). Potential impact of
new targeted drugs on testing probably in specific tumor subtypes such
as acral or mucosal melanoma will be discussed.
References
1 . Panel Members: M . Dietel (Berlin), A . Enk (Heidelberg), A . Lehmann (Berlin),
J .N . Bauer (Tübingen), C . Garbe (Tübingen), U . Kellner (Minden), T . Kirchner
(München), A . Jung (München), H . Kreipe (Hannover), S . Merkelbach-Bruse
(Köln), R . Büttner (Köln), W . Schlake (Gelsenkirchen), P . Schirmacher (Heidelberg),
R . Stadler (Minden) als Verfasser entsprechender Ankündigungspublikationen in
JDDG und Der Pathologe, eingereicht 2012 .
Ausgewählte Vorträge aus den Einsendungen
(Hauptprogramm und Arbeitsgemeinschaften)
AG Gastroenteropathologie I – Leber
DO-001a
miR-101 is involved in steatosis and steatohepatitis of Non-
Alcoholic Fatty Liver Disease (NAFLD)
K .S . Ommer1 , N . Elfimova1 , A . Noetel1 , H .-P . Dienes1 , M . Odenthal1 ,
N . Winkler 2 , M . Quasdorff2 , I . Strack1 , J . Riemer1 1 2 University Hospital of Cologne, Institute for Pathology, Köln, University
Hospital of Cologne, Department of Gastroenterology and Hepatology, Köln
Aims. The Non-Alcoholic Fatty Liver Disease (NAFLD) is a rising widespread
disease. Frequently, steatosis results in steatohepatitis (NASH),
however the factors, responsible for inflammatory progression, are yet
unknown. Since previous profiling studies have pointed to miR-101 as
a candidate involved in steatohepatitis, we have studied the role of miR-
101.
Der Pathologe · Supplement 1 · 2012 |
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