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

SA-P-011
Genetic aberrations of predictive factors are rare in triple-negative
breast cancer
T . Grob 1 , M . Choschzick 1 , G . Sauter 1 , A . Lebeau 1
1 University Medical Center Hamburg-Eppendorf, Institute of Pathology,
Hamburg
Aims. In the absence of estrogen as well as progesterone receptors and the
lack of HER2 amplification, women with triple-negative breast cancer
TNBC do not benefit from endocrine therapy or trastuzumab and are
left with chemotherapy as their only option. To reduce the elevated risk
of disease progression in these patients, better treatment options are needed
that are less toxic and are more targeted to this patient population.
Therefore, we performed a comprehensive analysis of potential targetable
genetic aberrations affecting the EGFR/HER2/MAPK pathway that
are observed at higher frequencies in adenocarcinomas of other organs.
Methods. 65 consecutive TNBCs were studied by sequence analysis for
HER2, EGFR, KRAS, BRAF mutations. TP53 sequence analysis was included
to control DNA quality and tumor cell content. A tissue microarray
(TMA) representing two samples of each tumor was constructed to
search for EGFR gene copy gain and EML4-ALK fusion by FISH. Triple
negative status was confirmed by immunohistochemistry (IHC) and
FISH on TMA sections. EGFR and CK5/6 IHC were added for identification
of the basal-like phenotype.
Results. Sequence analysis revealed HER2 gene mutation in one patient
(heterozygous missense mutation in exon 19: p.L755S). No mutations
were found in EGFR, KRAS and BRAF. High polysomy of EGFR was
detected in 5 of 62 informative cases by FISH. True EGFR gene amplification
accompanied by strong membraneous EGFR protein expression
was observed in only case. No rearrangement of the ALK gene was detected.
Basal-like phenotype was identified in 38 of the 65 TNBCs (58.5%).
TP53 mutations were detected in 36 of the 63 (57.1%) informative tumors.
Conclusions. Targetable genetic aberrations in the EGFR/HER2/MAPK
pathway occur rarely in TNBC. Nonetheless some patients might benefit
from HER2/EGFR targeted therapy.
SA-P-012
Luminal B breast cancers are not the end stage of a stepwise
dedifferentiation of luminal breast cancers
H . Bürger1 , B . Schymik2 , W . Meinerz2 , E . Korsching3 1University of Münster/Utrecht, Institute of Pathology, Paderborn, Paderborn,
2St .Vinzenz Hospital, Clinics of Gynecology, Paderborn, 3University of
Münster, Medical Faculty, Institute of Bioinformatics, Münster
Aims. Recent molecular data pointed towards the possibility of a stepwise
dedifferentiation in a subgroup of invasive breast cancer (BC) cases. In
detail, it was hypothesized, that estrogen receptor positive (ER+) grade
3 ductal invasive BC’s are the end stage of a dedifferentiation process of
luminal BC. A progression of luminal A towards luminal B breast cancers,
associated with a “progression through grade” seemed the obvious
explanation.
Methods. In order to verify this hypothesis on a morphological and
immunohistochemical level we investigated 865 invasive breast cancer
cases. All cases were reviewed for the presence of intratumoural heterogeneity
in the invasive cancer and the presence of associated ductal
carcinoma in situ (DCIS). With the use of tissue microarrays the molecular
subtype was determined and correlated with clinicopathological
features.
Results. We were able to show that regarding all breast cancer cases the
frequency of ER-positivity decreased with gain of tumour size. In detail,
the frequency of luminal A breast cancer decreased, whereas the number
of luminal B breast cancers remained constant. A constant increase of
the frequency of basal, HER2-driven and triple negative breast cancers
could be seen. Only in 1 out of 865 breast cancer cases a grade 1 and a
grade 3 invasive cancer component within the same breast cancer was
detectable. In 2 cases a ductal invasive grade 1 carcinoma was associated
with a poorly-differentiated DCIS. The frequency of cylinder cell lesions
was evenly distributed between ductal invasive grade 3 carcinomas, irrespectively
of the ER-status.
Conclusions. Our results show that a morphological recognizable “progression
through grade” is a very rare event in the natural course of invasive
breast cancer, including luminal breast cancer. If a progression
through grade occurs, this step is more likely located on the stage of ductal
carcinoma in situ or other suspected precursor lesions.
SA-P-013
Identification of a tissue-based protein signature associated
with triple negative breast cancer by imaging mass spectrometry
(MALDI Imaging)
C . Schöne1 , S . Rauser1 , S . Englert1 , S . Artmeier2 , K . Schulenburg2 , B . Balluff1 , M .
Elsner1 , S . Maier1 , S . Meding1 , M . Schmitt2 , H . Höfler3 , A . Walch1 1 2 Helmholtz Zentrum Munich, Institute of Pathology, Neuherberg, Klinikum
rechts der Isar of the Technische Universität München, Klinische Forschergruppe
of the Frauenklinik, Munich, 3Technische Universität München,
Institute of Pathology, Munich
Aims. The goal of this study is the identification of a tissue-based protein
signature associated with triple negative breast cancer for the purpose of
reliable classification and to identify potential new biomarkers.
Methods. A collective of 25 frozen triple negative and 44 non-triple negative
breast cancer samples was analysed in this study. Protein signatures
of the tissue samples were generated using MALDI Imaging with
a lateral resolution of 70 µM and a mass range of 2,500 to 25,000 Da.
Afterwards the cases were separated into a discovery set, containing 15
triple negative and 15 non-triple negative breast cancer cases, and a validation
set composed of the other cases. The mass spectra of the discovery
set were compared to each other to identify significantly differentially
expressed proteins. The resulting protein signature was then tested on
the validation set using different classification algorithms (divisive hierarchical
clustering, random forest or support vector machine).
Results. We were able to identify a signature composed of 10 different
proteins that could differentiate between triple negative and other breast
cancer samples with an accuracy of over 80%. Three of these proteins
were already encountered in a study dealing with HER2-overexpressing
breast cancer and are of special interest for identification.
Conclusions. MALDI Imaging made it possible to identify protein signatures
associated with triple negative breast cancer. The protein signature
may have potential for classification approaches and contains proteins
that may be of interest as potential biomarkers.
SA-P-014
Expression of RAD23B in invasive breast cancer.
Immunohistochemical study using tissue microarrays
K . Friedrich1 , A . Linge2 , F . Goerl1 , G . Baretton1 1University Hospital “Carl Gustav Carus” Dresden, Institute of Pathology,
Dresden, 2National Institute for Cellular Biotechnology, Dublin, Ireland
Aims. RAD23B is part of the nucleotide excision repair complex (NER)
and involved in repair of DNA damage caused by UV light exposure and
the chemotherapeutic drug cisplatin. The role of RAD23B expression in
invasive breast cancer is still unclear. Thus, the purpose of the study was
to analyse the RAD23B expression in correlation to clinicopathological
characteristics, proliferation and outcome of patients.
Methods. The expression of RAD23B, Ki67, HER-2/neu, estrogen and
progesterone receptor was analysed in 164 formalin fixed, paraffinembedded
specimens of invasive breast carcinoma using tissue microarrays.
All staining results were scored semiquantitatively. The mitotic
count was performed on H&E sections as was histopathological grading
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