Verhandlungen der Deutschen Gesellschaft fur Pathologie最新文献

{"title":"[Effective data collection in cancer research: an all-in-one database solution].","authors":"C Huszka,&nbsp;E Dahl,&nbsp;R Knüchel,&nbsp;A Donner","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Tissue banks containing human malignant and benign tissue have become highly important for modem cancer research. They provide an excellent source of information with respect to pathological states and processes. Nowadays tissue samples can be examined using a broad variety of molecular biology methods, at the levels of DNA, RNA and protein. However, these new possibilities impose great expectations from the user side towards tissue banks and their associated databases. Nowadays a database that only manages tissue samples is not timely anymore. In fact a modern database should be capable of registering arbitraty amounts of tissue relevant information in an easily searchable way. In order to simplify the often complicated and time consuming process of data collection, we have developed a software solution that centralizes various aspects of tumor tissue banking. The main task of this software is not only to administer tissue samples but also to provide a centralized data platform for scientists which support their research. To achieve our goals we have constructed a tissue database which is supported by an Oracle System. The access to this database has been made possible with a light-weight, self-developed Java Client Program. The system possesses high levels of security and the access to information in the database is strictly controlled by preset permissions. A flexible search mechanism is also readily available for speedy data extraction according to various criteria. This solution provides us with an \"All-in-one\" tool for the purpose of flexible and efficient data collection and management in cancer research.</p>","PeriodicalId":76792,"journal":{"name":"Verhandlungen der Deutschen Gesellschaft fur Pathologie","volume":"90 ","pages":"203-9"},"PeriodicalIF":0.0,"publicationDate":"2006-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40972863","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[A new quantitative DNA-methylation analysis of MSI colorectal cancers helps to separate sporadic colorectal cancers from HNPCC-candidates].","authors":"M Bettstetter,&nbsp;P Rümmele,&nbsp;F Hofstädter,&nbsp;W Dietmaier","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Aims: </strong>Promoter hypermethylation is a common mechanism for epigenetic control of gene expression and occurs frequently in tumors silencing tumor suppressor genes. Our aim was to establish a quantitative and precise method to analyze promoter methylation of tumor samples in order to identify HNPCC candidates.</p><p><strong>Methods: </strong>We established a new methylation specific relative quantitative real-time PCR technique for analysis of the methylation status of the hMLHI promoter in colorectal cancers (CRC). We determined methylation status of both the distal and proximal hMLH1-promoter region. The methylation quantification (MQ) was performed with cell line DNA and archival paraffinized tissue sections.</p><p><strong>Results: </strong>The accuracy of our analysis was validated with spiking experiments of methylated and unmethylated DNA. We assessed the hMLH1 methylation status 56 CRC patients with known microsatellite status and hMLH1 IHC. The methylation analysis divided the MSI-H CRC into two groups: Methylation positive sporadic CRC patients with a median age of 78.5 years and frequent BRAF mutations (82 %, p < 0.0001) and the unmethylated cancers from HNPCC candidates with a median age of 48 years. All hMLH1 positive sporadic MSS CRC were methylation negative. In all samples, the degree of methylation was mirrored by the shift of the melting points to higher temperatures.</p><p><strong>Conclusions: </strong>In summary we introduced a quantitative and qualitative technique to analyze DNA methylation that can be performed with any dense CpG island. Our methylation analysis provides a potent diagnostic tool to differentiate between sporadic MSI-H cancers showing MLH1 methylation and MLH1 unmethylated HNPCC candidates.</p>","PeriodicalId":76792,"journal":{"name":"Verhandlungen der Deutschen Gesellschaft fur Pathologie","volume":"90 ","pages":"236-43"},"PeriodicalIF":0.0,"publicationDate":"2006-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41040284","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Mutation of the FGFR3 oncogene is an independent and favorable prognostic factor for tumor-specific survival in patients with urothelial carcinoma of the upper urinary tract].","authors":"M Burger,&nbsp;J Catto,&nbsp;J van Oers,&nbsp;E Zwarthoff,&nbsp;F C Hamdy,&nbsp;M Meuth,&nbsp;A R Azzouri,&nbsp;O Cussenot,&nbsp;P J Wild,&nbsp;R Stoehr,&nbsp;A Hartmann","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Aims: </strong>Urothelial tumors of the upper urinary tract (UUTT) frequently display microsatellite Instability (MSI) and a distinct pathway of tumorigenesis resembling MMR-deficient colorectal cancers has been recognized for MSI-UUTT. For MSS-UUTT however oncogenic mechanisms as in bladder cancer (BC) are debated. Mutation of the oncogene FGFR3 has been linked to lower stage, lower grade and favourable clinical outcome in BC. The aim of this study was to evaluate FGFR3 mutation in MSI and MSS-UUTT.</p><p><strong>Methods: </strong>172 unselected UUTT were screened for MSI using the National Cancer Institute Consensus Panel and additional markers; FGFR3 status was studied using mutation analysis. Histopathological and clinical data were reviewed.</p><p><strong>Results: </strong>Microsatellite status had no impact on histopathological or clinical outcome. 52/99 MSS, 10/22 MSI-low and 25/51 MSI-high UUTT displayed mut. FGFR3 respectively. Overall FGFR3 mutation was associated with favourable stage and grade (p <0.0001 and p <0.002), as 62.1% of mut. vs. 23.5 % of wt. FGFR3 UUTT were stage Ta and T1 and graded G3 in 25.3 % vs. 47.1% respectively. That effect depended on MS-status however, as FGFR3 mutation was related to lower stage (pTa and pT1) in MSS/MSI-L (mut 62.9 % vs. wt 18.7%; p <0.01) only as opposed to MSI-H (mut 60% vs. wt. 50%; p = 0,1) UUTTs and as FGFR3 mut UUTTs tended to display lower grade (G1 and G2) provided stable (mut 74,2 % vs. wt. 44.1%; p <0,01) as opposed to instable microsatellite status (mut 76 % vs. wt. 73 %; p = 0.7). There was no marked relation of MS-status or FGFR3 mutation to sex, age or tobacco-exposure; localization in the renal pelvis (p < 0.01) however was more prevalent in the FGFR3 mut group. As opposed to MSI-status FGFR3 mutation had a favourable impact on survival, as 24.1% vs. 54.2 % cancer related deaths occured in the mutated group (p <0.001); this effect was indendent on stage or MSI-status. Neither MSI- nor FGFR3-status had any influence on subsequent bladder tumors.</p><p><strong>Conclusions: </strong>FGFR3 mutation is frequent in UUTT and appears to be independent of MS-status; however it is related to significantly favourable histopathological parameters and clinical outcome in MSS cases. Thus our findings might back the notion, that MSS and MSI-UUTTs stem from different oncogenic pathways and that their differing molecular character might have some relevance. Further research is warranted to study the clinical behavior of these tumors and to evaluate a potential role for MS-status and FGFR3 as prognostic tools.</p>","PeriodicalId":76792,"journal":{"name":"Verhandlungen der Deutschen Gesellschaft fur Pathologie","volume":"90 ","pages":"244-52"},"PeriodicalIF":0.0,"publicationDate":"2006-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41040285","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Molecular pathological analysis of neoplastic mast cells with regard to the actual WHO classification of mast cell neoplasias].","authors":"Karl Sotlar","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Detection of activating c-kit mutation D816 V is one of five criteria for the diagnosis of systemic mastocytosis (SM). The aims of this study were to (I) establish molecular methods for the detection of these mutations in paraffin-embedded biopsies, (II) determine the frequency of these mutations in mastocytoses and control tissues, (III) determine the frequency of these mutations in laser-microdissected lesional and nonlesional mast cells (MC), and (IV) investigate these matutions as a marker for clonality in cases with SM and associated clonal hematologic non-mast cell lineage diseases (SM-AHNMD). Formalin-fixed and paraffin-embedded biopsies of 48 patients with cutaneous mastocytosis (CM), 55 cases with various forms of SM, and 239 controls were investigated by PNA-mediated PCR-clamping. In addition, nested PCR amplified DNA of pooled microdissected single mast cells (MC) was investigated by melting point analysis. Activating c-kit mutation codon 816 mutations were detected in 38 % (18/48) of CM, in 91% (50/55) of SM, in 5 % (2/39) of MC hyperplasia and in none of 200 hematologic non-MC neoplasias. c-kit mutations were detected significantly more frequent in lesional MC as compared to non-lesional MC (p = 0,003). In 6/15 (40 %) cases with SM-AHNMD the same c-kit mutations were detected in microdissected MC and AHNMD cells. This study underlines the concept of the actual WHO classification of mastocytoses. By establishing methods for the detection of c-kit codon 816 mutations in paraffin-embedded tissues, the pathologist holds a central position in the diagnosis of systemic mastocytoses.</p>","PeriodicalId":76792,"journal":{"name":"Verhandlungen der Deutschen Gesellschaft fur Pathologie","volume":"90 ","pages":"227-35"},"PeriodicalIF":0.0,"publicationDate":"2006-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41040283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Aberrant promoter methylation as biomarker for molecular cytological diagnosis of lung cancer].","authors":"H J Grote","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Aberrant promoter methylation represents a main mechanism of tumor suppressor gene inactivation and may serve as a new source for biomarker discovery. This study investigated its applicability as a molecular tool for lung cancer diagnostics on bronchial aspirates. A methylation assay was developed applying a quantitative methylation specific real-time PCR (QMSP). A total of 552 patients with the differential diagnosis of lung cancer were investigated. The QMSP findings on bronchial aspirates were compared with the methylation status of respective genes investigated in microdissected tumor tissues (QMSP, cloning and sequencing of promoter regions after bisulfite conversion). Among the genes tested a marker panel consisting of APC, p16(INK4a) and RASSF1A proved to be the best suited for lung cancer diagnostics. This panel allowed for a correct diagnosis of lung cancer in cases with an ambiguous or false negative conventional cytology. In a cohort study on 247 patients, the combination of histology (sensitivity 59 %), cytology (sensitivity 44 %) and QMSP-assay (sensitivity 53 %) raised the sensitivity of a single bronchoscopy for the diagnosis of lung cancer up to 81%. The methylation assay yielded its major diagnostic surplus with respect to peripheral tumors representing 59 % of all primaries detected. In patients without antecedent lung cancer its specificity considering malignancy was >99 %. Therefore, the QMSP-assay is a promising technique which could enhance the sensitivity and diagnostic impact of conventional cytology. The assay is applicable to residual material of regular diagnostic cytology even in retrospect.</p>","PeriodicalId":76792,"journal":{"name":"Verhandlungen der Deutschen Gesellschaft fur Pathologie","volume":"90 ","pages":"216-26"},"PeriodicalIF":0.0,"publicationDate":"2006-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40972865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Omnis cellula e cellula--Pathology in Berlin 2006].","authors":"M Dietel","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":76792,"journal":{"name":"Verhandlungen der Deutschen Gesellschaft fur Pathologie","volume":"90 ","pages":"7-14"},"PeriodicalIF":0.0,"publicationDate":"2006-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40973003","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Global gene expression analysis and novel signalling pathways in Hodgkin lymphoma].","authors":"Andreas Bräuninger,&nbsp;Christoph Renné,&nbsp;Klaus Willenbrock,&nbsp;Jose Ignacio Martin-Subero,&nbsp;Nora Hinsch,&nbsp;Enrico Tiacci,&nbsp;Reiner Siebert,&nbsp;Ralf Küppers,&nbsp;Martin-Leo Hansmann","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>To identify pathogenetic mechanisms in Hodgkin lymphoma (HL) we performed global gene expression profiling of four HL derived cell lines and compared the expression profiles with those of normal B cells and B cell non-HL. This analysis revealed a global loss of B-cell specific gene expression in Hodgkin-Reed/Sternberg (HRS) cells (21). Further analysis showed that ABF-1 and Id2, which are both negative regulators of the B cell master transcription factor E2A and likely also Pax-5, are aberrantly expressed in HRS cell lines (11, 17). For Id2, immunohistochemistry showed expression in the HRS cells of all cases, and E2A could be coimmunoprecipitated with Id2 from HRS cell lines, indicating that the aberrant Id2 expression may indeed contribute to the loss of the B-cell specific gene expression in HL (17). An analysis of the global gene expression data for aberrant expression of genes which are frequently involved in neoplastic transformation identified six receptor tyrosine kinases (RTK) aberrantly expressed in HRS cell lines. All RTKs were also (co)-expressed in primary cases and mostly activated by auto- or paracrine mechanisms (18). Analysis of greater number of cases identified a subgroup of HL which encompasses about 20 % of cases characterised by coexpression of at least four of the RTKs. An survey of several B cell lymphoma types with a pan-phospho-tyrosine specific antibody indicated that mediastinal large B-cell lymphoma is beside HL the only entity where aberrant TK activities cause an aberrantly high cellular phospho-tyrosine content in a significant fraction of cases.</p>","PeriodicalId":76792,"journal":{"name":"Verhandlungen der Deutschen Gesellschaft fur Pathologie","volume":"90 ","pages":"136-41"},"PeriodicalIF":0.0,"publicationDate":"2006-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40970779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Parenchymal regression in chronic pancreatitis spares islets reprogrammed for expression of NFkappaB and IAPs].","authors":"Cornelia Hasel,&nbsp;Umesh K Bhanot,&nbsp;René Maier,&nbsp;Jörn Sträter,&nbsp;Peter Möller","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>In chronic pancreatitis (CP), fibrous replacement of exocrine tissue spares islets. There is local production of IFNgamma and death ligands by inflammatory cells as well as TGFbeta and TRAIL by pancreatic stellate cells (PSCs), along with functional death receptor neo-expression and apoptosis in exocrine but not in endocrine cells. Moreover, islets are strongly induced for TRAIL-receptor(R)-4 lacking a functional death domain. TRAIL-R4 signalling in T-cells induces NFkappaB transcription factors which activate anti-apoptotic programs. Whether TRAIL elicits this response in endocrine cells, we tested human insulinoma cell line CM and determined NFkappaB subunits transcripts and NFkappaB dependent inhibitor of apoptosis proteins (IAPs) in normal pancreas (NP) and CP. We treated CM with cytokines, determined TRAIL-R expression by flow cytometry, graded degree of fibrosis in CP specimens, microdissected epithelial compartments, performed real time PCRs for NFkappaB subunits transcripts, and immunohistochemistry for IKK-gamma, IkappaB-alpha, RelA, survivin, and cIAP1. In CM, TGFbeta/IFNgamma/TRAIL induced TRAIL-R4 surface expression. TRAIL/ IFNgamma, upregulated NFkappaB subunits and survivin while down-modulating 1kappaBalpha. NP epithelia had low RNA levels of NFkappaB subunits. These were increased in parenchymal areas of CP with severe fibrosis and most intensely in islets. The NFkappaB regulated proteins IkappaBalpha, survivin, and cIAP1 were found in corresponding sites, again, at highest levels in islets surrounded by fibrosis. In CP, islets not only evade immune attack by non-exposure of functional death receptors in presence of TRAIL-R4. They also neo-express NFkappaB subunits, survivin, and cIAP1. This apoptosis-inhibitory security program might be enforced by PSC-derived TRAIL.</p>","PeriodicalId":76792,"journal":{"name":"Verhandlungen der Deutschen Gesellschaft fur Pathologie","volume":"90 ","pages":"159-67"},"PeriodicalIF":0.0,"publicationDate":"2006-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40972858","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Cell-specific deletion of glucosylceramide synthase in brain leads to severe neural defects after birth].","authors":"R Jennemann,&nbsp;R Sandhoff,&nbsp;H Wiegandt,&nbsp;H-J Gröne","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Aims: </strong>Gangliosides, i. e. sialic acid containing glycosphingolipids, constitute a major component of neuronal cells and are thought to be essential for brain function. UDP-glucose: ceramide glucosyl-transferase (Ugcg) catalyzes the initial step of glycosphingolipid (GSL) biosynthesis. A total deletion of the Ugcg-gene in mice led to embryonic lethality. In order to gain insight into the role of gangliosides in brain development and function, a cell specific disruption of Ugcg was performed.</p><p><strong>Methods: </strong>A cell specific disruption of Ugcg in mice was performed using the Cre/loxP-system. LoxP-flanked Ugcg-mice were generated and crossed with nestin-cre mice.</p><p><strong>Results: </strong>The nestin-promoted gene deletion in neuronal cells was indicated by the absence of virtually all gangliosides already at stage E15.5. Shortly after birth mice showed dysfunction of cerebellum and peripheral nerves, associated with structural defects. Axon-branching of Purkinje cells was significantly reduced. In primary cultures of neurons dendritic complexity was clearly diminished, while pruning occurred. Myelin sheaths of peripheral nerves were broadened and focally severely disorganized. GSL deficiency also led to a downregulation of gene expression sets involved in brain development and homeostasis. Mice died approximately 3 weeks after birth.</p><p><strong>Conclusions: </strong>The pronounced neurologic symptoms in postnatal mice with neuronal specific deficiency of glucosylceramide synthesis demonstrate that GlcCer-derived GSL may not serve functions essential for early brain development. They are, however, required for neuron differentiation and brain maturation.</p>","PeriodicalId":76792,"journal":{"name":"Verhandlungen der Deutschen Gesellschaft fur Pathologie","volume":"90 ","pages":"193-202"},"PeriodicalIF":0.0,"publicationDate":"2006-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40972862","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Soft tissue sarcomas: the role of histology and molecular pathology for differential diagnosis].","authors":"C Poremba","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Soft tissue sarcomas include a wide spectrum of different entities. The so-called small round blue cell tumors and spindle cell tumors are difficult to classify based solely on conventional histology. To identify different subtypes of tumors special histochemical and immunohistochemical techniques are necessary. Analysis of protein expression by immunohistochemistry provides a helpful tool to investigate the histogenesis of tumors. A basic spectrum of antibodies should be included to study these tumors: Desmin and myogenin (or MyoD1) for skeletal differentiation; S-100, NSE, CD56, and synaptophysin for neural/neuroendocrine differentiation; CD3, CD20, and CD79 alpha for malignant lymphomas; CD34, sm-actin, and beta-catenin for spindle cell tumors; additional antigens, e. g. Ki-67 and p 53, for estimation of proliferation and tumor suppressor gene malfunctions. Nevertheless, the molecular analysis of soft tissue sarcomas is necessary for demonstration of specific translocations or gene defects to specify and proof a diagnosis. For this purpose, RT-PCR for RNA expression analysis of gene fusion transcripts and multi-color FISH for analysis of chromosomal rearrangements are used. Further investigations, using DNA microrrays may help to subclassify such tumors, with respect to prognosis or prediction of therapeutic response.</p>","PeriodicalId":76792,"journal":{"name":"Verhandlungen der Deutschen Gesellschaft fur Pathologie","volume":"90 ","pages":"59-72"},"PeriodicalIF":0.0,"publicationDate":"2006-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40972950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}