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

More documents

Recommendations

Info

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 Der Pathologe · Supplement 1 · 2012 | 143
Abstracts according to Elston & Ellis. The statistical analysis was done by Chisquared test, t-Test according to student, Kaplan-Meier estimation and multivariate discriminant analysis. Results. Nuclear expression of RAD23B was observed in all analysed cases, ranging from 5–90% of tumor cells with different intensities. RAD23B expression was correlated with age, histopathological grade and mitotic activity in univariate analyses. Patients with a disease manifestation after the age of fifty showed a lower RAD23B expression than younger patients. A histopathological grade 1 or 2 was associated with a higher RAD23B expression. The mitotic activity was lower in cases with high RAD23B expression. The mitotic activity was lower in cases with high RAD23B expression than in cases with low RAD23B expression. The multivariate analysis revealed mitotic activity and Ki67 expression as significant markers. There was no correlation between RAD23B expression and the other clinicopathological markers or the outcome of disease. Conclusions. The correlation of RAD23B expression to proliferation, especially to mitotic activity may be associated with the function of RAD23B and the binding of RAD23, XPC and Centrin 2 in DNA damage recognition complex. Its role in repair of cisplatin-damaged DNA suggests that RAD23B may be used as a predictive marker for response to cisplatin based chemotherapy. SA-P-015 Up-regulation of Kindlin-2 promotes progression of human breast cancer cells by increasing their proliferation, drug resistance, genomic instability, and tumorigenesis W .-g . Fang1 , T . Zhao1 , H .-q . Zhang1 1Peking University, Health Science Center, Beijing, China Aims. Kindlin-2 has been confirmed as an essential element of bidirectional integrin signaling. In recent years, the relationship between Kindlin-2 expression and cancers has been a focus of interest. Our previous studies have shown that Kindlin-2 expression was up-regulated in several types of human cancers, and a strong correlation between Kindlin-2 expression and clinical outcome of breast cancer patients was found. However, the functional role of Kindlin-2 in breast cancer has not been studied. This study was designed to investigate the role of Kindlin-2 in the progression of human breast cancer cells. Methods. Firstly, Kindlin-2 expression at protein level was detected by Western blot in several breast cancer cell lines. Two luminal-like breast cancer cell lines, MCF-7 and T47D, expressed low level of Kindlin-2. Two basal-like breast cancer cell lines, MDA-MB-231 and HS578T, expressed moderate levels of the protein. Then, Kindlin-2 gene was overexpressed by transfected into MCF-7 cells. In comparison, short hairpin RNA (ShRNA)-mediated knockdown of Kindlin-2 was performed in HS578T cells. Vector controls were also done in the same cell lines. Ki67 Li, FCM cell cycle, anchorage-independent colony formation (in vitro tumorigenesis), and in vivo tumorigenesis in NOD/SCID mice were observed. Apoptotic cells were labeled by fluorescent annexin V assay and quantified by FACS. Array CGH analysis and spectral karyotyping were performed to detect the genomic instability of these cells. Results. The growth rate of Kindlin-2-transfected MCF-7 cells was much quicker than that of the controls. The proportion of G2-M phase cells, clone formation and tumorigenicity were significantly higher than these of the controls. The change of Kindlin-2-ShRNA transfected cells was just the reverse. Moreover, Up-regulation of Kindlin-2 can also reduce the rate of apoptosis induced by the chemotherapy drugs, and these cells showed much more genomic instability compared with the controls. Conclusions. These findings suggested that up-regulation of Kindlin-2 promotes the progression of human breast cancer cells by increasing their proliferation, drug resistance, genomic instability, and tumorigenesis. 144 | Der Pathologe · Supplement 1 · 2012 SA-P-016 GPR30: a predictive marker for Tamoxifen resistance in breast cancer T . Kalinski1 , A . Roessner2 , S .-D . Costa2 , A . Ignatov2 1Otto-von-Guericke-University/Department of Pathology, Magdeburg, 2 Magdeburg Aims. Tamoxifen is the gold standard in the therapy of hormone-dependent breast cancer. However, the development of Tamoxifen resistance is a frequent problem in Tamoxifen-responsive tumors during treatment. The aim was to investigate the role of the new estrogen receptor GPR30 in the development of Tamoxifen resistance. Methods. Mechanisms of Tamoxifen resistance were investigated in Tamoxifen-resistant breast cancer cells and wild type cells. The expression of GPR30 was further analyzed in breast cancer specimens and correlated with clinical data. Results. The results proved the important role of GPR30 in the development of Tamoxifen resistance in breast cancer. GPR30 expression in breast cancer specimens was associated with Tamoxifen resistance and negatively correlated with relapse free survival in patients treated with Tamoxifen. Conclusions. GPR30 plays an important role in the development of Tamoxifen resistance in breast cancer cells. GPR30 expression is a predictive marker for the development of Tamoxifen resistance in breast cancer specimens. SA-P-017 CD34+ fibrocytes in the stroma of ductal carcinoma in situ (DCIS) of the breast P .J . Barth1 , F . Wötzel1 1University Hospital Münster, Institute of Pathology, Münster Aims. Im Stroma normalen Brustdrüsengewebes finden sich überwiegend CD34+-Fibrozyten, die eine große Rolle in der Matrixsynthese und bei der Aufrechterhaltung der Integrität des mammären Stromas spielen. Zudem spielen CD34+ Fibrozyten eine Rolle als Antigen präsentierende Zellen. Das Stroma invasiver duktaler Karzinome zeigt einen kompletten Verlust der stromalen CD34-Expression und einen Phänotypwechsel der Stromazellen von CD34+SMA−Fibrozyten zu CD34−SMA+-Myofibroblasten. Bisher wurden keine Studien zur CD34 Expression im Stroma von DCIS durchgeführt. Methods. Wir untersuchten DCIS unterschiedlichen Kernmalignitätsgrades immunhistochemisch bezüglich der stromalen Expression von CD34, SMA (Glattmuskel-Aktin) und SMM (Glattmuskel-Myosin). Es wurden nur DCIS untersucht, die nicht mit einem invasiven Karzinom assoziiert waren. In jedem Fall lag tumorfreies Brustdrüsengewebe zum Vergleich vor. Results. Tumorfreies Brustdrüsengewebe zeigte periduktal und periazinär dicht gelagerte CD34+ Fibrozyten mit bipolaren zarten Zytoplasmafortsätzen. SMA+ Stromazellen wurden in tumorfreiem, normalem Brustdrüsengewebe nicht beobachtet. DCIS niedrigen und mittleren Kernmalignitätsgrades zeigten eine erhaltene Population von CD34+ Fibrozyten, SMA+ Zellen wurden im Stroma nicht beobachtet. DCIS hohen Kernmalignitätsgrades zeigten einen Verlust periduktaler CD34+ Fibrozyten; an ihrer Stelle zeigten sich CD34-SMA+ Myofibroblasten, die konzentrisch um die vom DCIS befallenen Ductus angeordnet waren. Conclusions. Diese Untersuchung zeigt, dass es bei DCIS hohen Kernmalignitätsgrades zu Veränderungen des Stromas kommt, die auch bei invasiven Karzinomen gefunden wurden. Der Verlust der CD34+ Fibrozyten führt zu einer Störung der Integrität des Stromas, die Voraussetzung für die Entstehung eines invasiven Karzinoms sein kann. Zudem kann der Verlust der CD34+ Fibrozyten, bei denen es sich um Antigen präsentierende Zellen handelt, zu einer Störung der gegen Tumorzellen gerichteten Immunkontrolle des Organismus führen. Beides sind
Page 2 and 3:
Inhalt Der Pathologe · Supplement
Page 4 and 5:
Inhalt Der Pathologe · Supplement
Page 6 and 7:
Editorial Liebe Kolleginnen und Kol
Page 8 and 9:
Kolorektales Karzinom 2 VO-005 Tran
Page 10 and 11:
Keynote Lecture VO-014 Genetic dete
Page 12 and 13:
(AMACR, FASN, GOLM1, GSP-pi, ERG) t
Page 14 and 15:
to assess the correct rate of R1 re
Page 16 and 17:
DNA damage, and cytotoxic drugs. Au
Page 18 and 19:
HCV-positive formalin-fixed and par
Page 20 and 21:
well as MET activation were examine
Page 22 and 23:
or BRAF mutation, c-MYC and SIRT1 e
Page 24 and 25:
AG Pneumopathologie III DO-032 Remo
Page 26 and 27:
immature granulopoiesis showed a st
Page 28 and 29:
ned, if well-defined mantle zones,
Page 30 and 31:
phomas). Most prominent gains or am
Page 32 and 33:
DO-062 Tumor-associated macrophages
Page 34 and 35:
DO-080 DOG1: an immunohistochemical
Page 36 and 37:
AG Oralpathologie DO-087 Detection
Page 38 and 39:
DO-094 Do activated fibroblasts inf
Page 40 and 41:
DO-101 Histopathological analysis o
Page 42 and 43:
DO-108 Identification of potential
Page 44 and 45:
Conclusions. In conclusion, 454 par
Page 46 and 47:
subgroup of patients with B-Raf mut
Page 48 and 49:
DO-002b Impact of terminologies in
Page 50 and 51:
Methods. We performed MCPyV-FISH of
Page 52 and 53:
FR-013 HPV-genotype distribution in
Page 54 and 55:
Methods. Three different techniques
Page 56 and 57:
(i.e. investment in equipment and e
Page 58 and 59:
FR-032 COLD-PCR: a powerful tool in
Page 60 and 61:
dissection (MBLND) technique to imp
Page 62 and 63:
SO-005 Prevalence of mutations in s
Page 64 and 65:
SO-011 Methylation profiling and in
Page 66 and 67:
more effective than SAHA alone and
Page 68 and 69:
SO-022 Specialized pathology review
Page 70 and 71:
SO-027 Ki-67 in mitotic score group
Page 72 and 73:
nificantly associated with advanced
Page 74 and 75:
liver did not correlate with the mu
Page 76 and 77:
AG Paidopathologie II SO-046 Overex
Page 78 and 79:
Results. Histomorphology of the ova
Page 80 and 81:
p42 and p27 have not yet been inves
Page 82 and 83:
SO-068 Recent advances in understan
Page 84 and 85:
SO-075 A novel, dual role of CCN3 i
Page 86 and 87:
Pancreatic Adenocarcinoma SG-137 Se
Page 88 and 89:
sease and 30 colon cancer serum sam
Page 90 and 91:
Conclusions. Although CRC is charac
Page 92 and 93:
differentiated and TNM stage III or
Page 94 and 95: pressed moderate levels of the prot
Page 96 and 97: FR-P-037 MALDI imaging reveals COX7
Page 98 and 99: in the context of therapy response
Page 100 and 101: on primary cells of wild-type and c
Page 102 and 103: chemotherapy was recommended and co
Page 104 and 105: aims are twofold: 1) to verify the
Page 106 and 107: Results. Her2/neu status in TMAs an
Page 108 and 109: prognostic impact was found in rect
Page 110 and 111: provided information on survival ti
Page 112 and 113: Methods. Biopsy specimens from 430
Page 114 and 115: the OS rate was 53% for patients wi
Page 116 and 117: FR-P-098 Immunohistological stainin
Page 118 and 119: FR-P-104 Histopathological evaluati
Page 120 and 121: within the earliest morphologic det
Page 122 and 123: Conclusions. In primary imaging a g
Page 124 and 125: fibrotic neointma development as we
Page 126 and 127: FR-P-129 Alpha-1-antitrypsin-PiZ-an
Page 128 and 129: FR-P-136 The expression of central
Page 130 and 131: cosa and in the periarterial tissue
Page 132 and 133: FR-P-149 Combination of Castleman d
Page 134 and 135: or without different concentrations
Page 136 and 137: Results. In 18 cases (79%) the caus
Page 138 and 139: FR-P-168 Autopsy findings in a 2-ye
Page 140 and 141: FR-P-174 MPGN-like glomerulonephrit
Page 142 and 143: Poster: Gynäkopathologie und Mamma
Page 146 and 147: Mechanismen, die eine Progression d
Page 148 and 149: internet server. A network of inter
Page 150 and 151: Methods. HE-gefärbte Schnittpräpa
Page 152 and 153: Conclusions. The newly released 450
Page 154 and 155: and desmoplastic reaction are diffe
Page 156 and 157: one patient revealed more than 9 mi
Page 158 and 159: situation, the V600E mutation in th
Page 160 and 161: SA-P-064 Evolution of molecular pat
Page 162 and 163: nic markers such as myf4 and MyoD1
Page 164 and 165: Conclusions. To our knowledge, this
Page 166 and 167: SA-P-085 Expression of the eukaryot
Page 168 and 169: Results. The papillary RCC type II
Page 170 and 171: SA-P-098 Male infertility: assessme
Page 172 and 173: SA-P-104 Process oriented scientifi
Page 174 and 175: Conclusions. The IBDW offers a uniq
Page 176 and 177: L Lasitschka F. DO-046 Lehmann A. F
show all

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

You also want an ePaper? Increase the reach of your titles

Delete template?

Save as template?