Rüschoff, Josef R.

[["dc.bibliographiccitation.firstpage","550"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","British Journal of Surgery"],["dc.bibliographiccitation.lastpage","557"],["dc.bibliographiccitation.volume","101"],["dc.contributor.author","Homayounfar, Kia"],["dc.contributor.author","Bleckmann, Annalen"],["dc.contributor.author","Helms, H.-J."],["dc.contributor.author","Lordick, Florian"],["dc.contributor.author","Rueschoff, Josef"],["dc.contributor.author","Conradi, L.-C."],["dc.contributor.author","Sprenger, T."],["dc.contributor.author","Ghadimi, Michael B."],["dc.contributor.author","Liersch, Thorsten"],["dc.date.accessioned","2018-11-07T09:41:56Z"],["dc.date.available","2018-11-07T09:41:56Z"],["dc.date.issued","2014"],["dc.description.abstract","Background: Multidisciplinary discussion of the treatment of patients with colorectal liver metastases (CRLM) is advocated currently. The aim of this study was to investigate medical oncologists' and surgeons' assessment of resectability and indication for chemotherapy, and the effect of an educational intervention on such assessment. Methods: Medical histories of 30 patients with CRLM were presented to ten experienced medical oncologists and 11 surgeons at an initial virtual tumour board meeting (TB1). Treatment recommendations were obtained from each participant by voting for standardized answers. Following lectures on the potential of chemotherapy and surgery, assessment was repeated at a second virtual tumour board meeting (TB2), using the same patients and participants. Results: Overall, 630 answers (21 x 30) were obtained per tumour board meeting. At TB1, resectability was expected more frequently by surgeons. Participants changed 56.8 per cent of their individual answers at TB2. Assessment shifted from potentially resectable to resectable CRLM in 81 of 161 and from unresectable to (potentially) resectable CRLM in 29 of 36 answers. Preoperative chemotherapy was indicated more often by medical oncologists, and overall was included in 260 answers (41.3 per cent) at TB1, compared with only 171 answers (27.1 per cent) at TB2. Medical oncologists more often changed their decision to primary resection in resectable patients (P = 0.006). Postoperative chemotherapy was included in 51.9 and 52.4 per cent of all answers at TB1 and TB2 respectively, with no difference in changes between medical oncologists and surgeons (P = 0.980). Conclusion: Resectability and indication for preoperative chemotherapy were assessed differently by medical oncologists and surgeons. The educational intervention resulted in more patients deemed resectable by both oncologists and surgeons, and less frequent indication for chemotherapy."],["dc.description.sponsorship","Merck Serono GmbH, Germany"],["dc.identifier.doi","10.1002/bjs.9436"],["dc.identifier.isi","000332700100017"],["dc.identifier.pmid","24756914"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/33842"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-blackwell"],["dc.relation.issn","1365-2168"],["dc.relation.issn","0007-1323"],["dc.title","Discrepancies between medical oncologists and surgeons in assessment of resectability and indication for chemotherapy in patients with colorectal liver metastases"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","11"],["dc.bibliographiccitation.journal","Cancer Epidemiology Biomarkers & Prevention"],["dc.bibliographiccitation.volume","14"],["dc.contributor.author","Heinmoller, E."],["dc.contributor.author","Werther, M."],["dc.contributor.author","Baumgart, M."],["dc.contributor.author","Ziemer, M."],["dc.contributor.author","Ruschoff, J."],["dc.contributor.author","Ghadimi, Michael B."],["dc.date.accessioned","2018-11-07T10:54:31Z"],["dc.date.available","2018-11-07T10:54:31Z"],["dc.date.issued","2005"],["dc.format.extent","2740S"],["dc.identifier.isi","000233351200243"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/49581"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Assoc Cancer Research"],["dc.publisher.place","Philadelphia"],["dc.relation.conference","4th Annual Conference on Frontiers in Cancer Prevention Research"],["dc.relation.eventlocation","Baltimore, MD"],["dc.relation.issn","1055-9965"],["dc.title","Aneuploidy together with heterozygous mutations of tumor suppressor genes p53 and p16 can be found in early preneoplastic lesions in chronic pancreatitis suggesting a clonal expansion during progression."],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1093"],["dc.bibliographiccitation.issue","7"],["dc.bibliographiccitation.journal","Pancreas"],["dc.bibliographiccitation.lastpage","1103"],["dc.bibliographiccitation.volume","39"],["dc.contributor.author","Baumgart, Mario"],["dc.contributor.author","Werther, Meike"],["dc.contributor.author","Bockholt, Anke"],["dc.contributor.author","Scheurer, Maria"],["dc.contributor.author","Rueschoff, Josef"],["dc.contributor.author","Dietmaier, Wolfgang"],["dc.contributor.author","Ghadimi, B. Michael"],["dc.contributor.author","Heinmoeller, Ernst"],["dc.date.accessioned","2018-11-07T08:38:53Z"],["dc.date.available","2018-11-07T08:38:53Z"],["dc.date.issued","2010"],["dc.description.abstract","Objective: Chronic pancreatitis (CP) is a predisposing disease for pancreatic carcinoma (PC), however, precise molecular mechanisms of cancer development in the background of CP are ill defined. Methods: A total of 443 laser-microdissected pancreatic intraepithelial neoplasias (PanINs), acinar-ductal metaplasia (ADM), and normal ducts from 21 patients with CP were analyzed for loss of heterozygosity (LOH) and immunohistochemical protein expression of p53, p16, and DPC4. Pancreatic intraepithelial neoplasias were analyzed for mutations in p53, p16, and Ki-ras genes by ABI sequencing. Aneuploidy was determined by fluorescence in situ hybridization with probes for chromosomes 3, 7, 8, and 17. Results: Loss of heterozygosity rate in PanIN-1 and ADM was between 1.7% (p53) and 5.8% (p16). In PanIN-3, p53 protein overexpression and loss of expression for p16 and DPC4 protein were seen. Heterozygous mutations of p53 and p16 without LOH were found in PanIN-1A and ADM, whereas homozygous mutations were found in PanIN-3. Aneuploidy increased from PanIN-1A to PanIN-3. Ki-ras mutations were discovered first in PanIN-1. Conclusions: Heterozygous mutations of p53-and p16 genes together with chromosomal instability occur early in CP and are clonally expanded, but final inactivation mostly by LOH happens later in pancreatic carcinogenesis. Determination of aneuploidy in pancreatic juice may be of value for early detection and risk assessment in patients with long-standing CP."],["dc.description.sponsorship","German Research Foundation [Gh 14-2/1]; Matthias Lackas Stiftung"],["dc.identifier.doi","10.1097/MPA.0b013e3181dc62f6"],["dc.identifier.isi","000282098200024"],["dc.identifier.pmid","20531246"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/18862"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Lippincott Williams & Wilkins"],["dc.relation.issn","0885-3177"],["dc.title","Genomic Instability at Both the Base Pair Level and the Chromosomal Level Is Detectable in Earliest PanIN Lesions in Tissues of Chronic Pancreatitis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","564"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Surgery"],["dc.bibliographiccitation.lastpage","570"],["dc.bibliographiccitation.volume","151"],["dc.contributor.author","Jo, Peter"],["dc.contributor.author","Jung, Klaus"],["dc.contributor.author","Grade, Marian"],["dc.contributor.author","Conradi, Lena-Christin"],["dc.contributor.author","Wolff, Hendrik Andreas"],["dc.contributor.author","Kitz, Julia"],["dc.contributor.author","Becker, Heinz"],["dc.contributor.author","Rüschoff, Josef R."],["dc.contributor.author","Hartmann, Arndt"],["dc.contributor.author","Beißbarth, Tim"],["dc.contributor.author","Müller-Dornieden, Annegret"],["dc.contributor.author","Ghadimi, Michael B."],["dc.contributor.author","Schneider-Stock, Regine"],["dc.contributor.author","Gaedcke, Jochen"],["dc.date.accessioned","2018-11-07T09:11:55Z"],["dc.date.available","2018-11-07T09:11:55Z"],["dc.date.issued","2012"],["dc.description.abstract","Background. Locally advanced rectal cancers are treated with preoperative radiochemotherapy (RCT). However, subsets of patients have no benefit from preoperative treatment. Since epigenetic modifications, including DNA methylation, may influence response to neoadjuvant treatment we studied the CpG island methylator phenotype (CIMP) in patients who received a 5-fluouracil based RCT Methods. One hundred fifty patients, with locally advanced rectal cancer, treated within a phase HI clinical trial (CAO/ARO/AIO-94 and -04), were included in this analysis. CIMP was assessed by methylation specific PCR (MSP) using RUNX3, SOCS1, NEUROG1, IGF2, and CACNA1G as a marker panel. Loss of mismatch repair gene (MMR) expression was assessed by immunohistochemistry for a subset of patients. KRAS and BRAF mutation status were assessed using Sanger sequencing. Results. The CIMP status could be established in all 150 patients. Fifteen (10%) revealed CIMP positivity >= 3 methylated promoters), whereas 135 patients (90%) where classified as CIMP negative. Analysis for MMR status. did not reveal any microsatellite instability (MSI). A single mutation of the BRAF gene (D594G) was detected. The KRAS gene (exon 1, 2, and 3) was mutated in 65 tumors (43%) but was not correlated to a specific CIMP status. Three- and 5-year disease-free survival was notably worse in CIMP positive patients (56% and 0% vs 80% and 75%; P < .01) suggesting an increased likelihood of poor clinical outcome (HR 5.5; 95% CI: [2.1, 13.9]). Conclusion. CIMP positivity, defined by methylation of at least 3 specific gene promoters, is an infrequent event in locally advanced rectal cancer. However it increases the likelihood of distant metastases. Therefore, the CIMP status may be included as a molecular marker for the identification of high-risk patients and might contribute to individual treatment stratification. (Surgery 2012;151:564-70.)"],["dc.identifier.doi","10.1016/j.surg.2011.08.013"],["dc.identifier.isi","000301996600010"],["dc.identifier.pmid","22001634"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/26829"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Mosby-elsevier"],["dc.relation.issn","0039-6060"],["dc.title","CpG island methylator phenotype infers a poor disease-free survival in locally advanced rectal cancer"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","522"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","American Journal of Surgical Pathology"],["dc.bibliographiccitation.lastpage","531"],["dc.bibliographiccitation.volume","37"],["dc.contributor.author","Conradi, Lena-Christin"],["dc.contributor.author","Styczen, Hanna"],["dc.contributor.author","Sprenger, Thilo"],["dc.contributor.author","Wolff, Hendrik Andreas"],["dc.contributor.author","Roedel, Claus"],["dc.contributor.author","Nietert, Manuel M."],["dc.contributor.author","Homayounfar, Kia"],["dc.contributor.author","Gaedcke, Jochen"],["dc.contributor.author","Kitz, Julia"],["dc.contributor.author","Talaulicar, Recca"],["dc.contributor.author","Becker, Heinz"],["dc.contributor.author","Ghadimi, Michael B."],["dc.contributor.author","Middel, Peter"],["dc.contributor.author","Beißbarth, Tim"],["dc.contributor.author","Rüschoff, Josef R."],["dc.contributor.author","Liersch, Torsten"],["dc.date.accessioned","2018-11-07T09:26:46Z"],["dc.date.available","2018-11-07T09:26:46Z"],["dc.date.issued","2013"],["dc.description.abstract","In patients with advanced rectal cancer (cUICC II and III) multimodality therapy resulted in better long-term local tumor control. Ongoing clinical trials are focusing on therapy intensification to improve disease-free (DFS) and cancer-specific survival (CSS), the integration of biomarkers for prediction of individual recurrence risk, and the identification of new targets. In this context, we investigated HER-2, a member of the epidermal growth factor receptor family, whose expression pattern and role was unclear in rectal cancer. A total of 264 patients (192 male, 72 female; median age 64 y) received standardized multidisciplinary treatment according to protocols of phase II/III trials of the German Rectal Cancer Study Group. HER-2 status was determined in pretherapeutic biopsies and resection specimens using immunohistochemistry scoring and detection of silver in situ hybridization amplification. Tumors with an immunohistochemistry score of 3(+) or silver in situ hybridization ratios of >= 2.0 were classified HER-2 positive; these results were correlated with clinicopathologic parameters [eg, resection (R) status, nodal status ((y)pN)], DFS, and CSS. Positive HER-2 status was found in 12.4% of biopsies and in 26.7% of resected specimens. With a median follow-up of 46.5 months, patients with HER-2 positivity showed in trend a better DFS (P = 0.1) and a benefit in CSS (P = 0.03). The 5-year survival rate was 96.0% (HER-2 positive) versus 80.0% (HER-2 negative). In univariate and multivariate analyses, HER-2 was an independent predictor for CSS (0.02) along with the (y)pN status (P < 0.00001) and R status (P = 0.011). HER-2 amplification is detectable in a relevant proportion (26.7%) of rectal cancer patients. For the development of innovative new therapies, HER-2 may represent a promising target and should be further assessed within prospective clinical trials."],["dc.description.sponsorship","Deutsche Forschungsgemeinschaft [KFO 179-2]"],["dc.identifier.doi","10.1097/PAS.0b013e318272ff4d"],["dc.identifier.isi","000316184000006"],["dc.identifier.pmid","23282976"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/30374"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Lippincott Williams & Wilkins"],["dc.relation.issn","1532-0979"],["dc.relation.issn","0147-5185"],["dc.title","Frequency of HER-2 Positivity in Rectal Cancer and Prognosis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","458"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","Journal of Clinical Pathology"],["dc.bibliographiccitation.lastpage","464"],["dc.bibliographiccitation.volume","68"],["dc.contributor.author","Scheel, Andreas Hans"],["dc.contributor.author","Reineke, Rebecca A."],["dc.contributor.author","Sprenger, Thilo"],["dc.contributor.author","Lokka, Suvi"],["dc.contributor.author","Kitz, Julia"],["dc.contributor.author","Ghadimi, B. Michael"],["dc.contributor.author","Rueschoff, Josef"],["dc.contributor.author","Liersch, Torsten"],["dc.contributor.author","Middel, Peter"],["dc.date.accessioned","2018-11-07T09:56:45Z"],["dc.date.available","2018-11-07T09:56:45Z"],["dc.date.issued","2015"],["dc.description.abstract","Aims Acetone compression (AC) is an elution compression technique for the comprehensive pathological examination of fatty tissue. Here AC is combined with digital morphometry to evaluate the impact of preoperative (neoadjuvant) chemoradiotherapy (neoCRT) on lymph node (LN) numbers and morphology in locally advanced rectal cancer. AC is compared with complete embedding of the mesorectal fat (whole mesorectal embedding (WME)) to exclude artificial alterations and to the standard technique, manual dissectioning (MD). Methods 320 rectal cancer specimens were subjected to LN morphometry. Neoadjuvant CRT was applied in 204 specimens. LNs were prepared either with AC (n=138), WME (n=51) or MD (n=131). 8523 LNs were assessed including 530 nodes with metastases. Results LN prepared by AC and WME showed similar morphologies. AC revealed reduced LN sizes in neoCRT specimens compared with primary resection (2.2; 2.4 mm, p=0.049) while the LN number was comparable (27; 30/specimen). AC yielded 28 LN/specimen on average, MD yielded 22 LN (p<0.001). In neoCRT specimens, MD yielded less LN compared with primary resection (19; 25). MD detected less small LN (<2 mm; MD: 25%; AC: 56%) while 24 of the 135 LN metastases found by AC were <= 2 mm in diameter. Conclusions AC does not alter LN morphology and is especially suited to retrieve small LN after neoadjuvant CRT of rectal cancer. Neoadjuvant multimodality treatment caused reduced LN sizes while the LN numbers were not affected. When compared with MD, AC proved more reliable in the retrieval of LN from rectal cancer specimens after neoCRT."],["dc.description.sponsorship","Deutsche Forschungsgemeinschaft [KFO179]"],["dc.identifier.doi","10.1136/jclinpath-2014-202555"],["dc.identifier.isi","000354653500013"],["dc.identifier.pmid","25779094"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/37025"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Bmj Publishing Group"],["dc.relation.issn","1472-4146"],["dc.relation.issn","0021-9746"],["dc.title","Comprehensive lymph node morphometry in rectal cancer using acetone compression"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","e101563"],["dc.bibliographiccitation.issue","7"],["dc.bibliographiccitation.journal","PLOS ONE"],["dc.bibliographiccitation.volume","9"],["dc.contributor.author","Ilgen, Peter"],["dc.contributor.author","Stoldt, Stefan"],["dc.contributor.author","Conradi, Lena-Christin"],["dc.contributor.author","Wurm, Christian Andreas"],["dc.contributor.author","Rüschoff, Josef"],["dc.contributor.author","Ghadimi, B. Michael"],["dc.contributor.author","Liersch, Torsten"],["dc.contributor.author","Jakobs, Stefan"],["dc.date.accessioned","2017-09-07T11:45:42Z"],["dc.date.available","2017-09-07T11:45:42Z"],["dc.date.issued","2014"],["dc.description.abstract","Formalin fixed and paraffin-embedded human tissue resected during cancer surgery is indispensable for diagnostic and therapeutic purposes and represents a vast and largely unexploited resource for research. Optical microscopy of such specimen is curtailed by the diffraction-limited resolution of conventional optical microscopy. To overcome this limitation, we used STED super-resolution microscopy enabling optical resolution well below the diffraction barrier. We visualized nanoscale protein distributions in sections of well-annotated paraffin-embedded human rectal cancer tissue stored in a clinical repository. Using antisera against several mitochondrial proteins, STED microscopy revealed distinct sub-mitochondrial protein distributions, suggesting a high level of structural preservation. Analysis of human tissues stored for up to 17 years demonstrated that these samples were still amenable for super-resolution microscopy. STED microscopy of sections of HER2 positive rectal adenocarcinoma revealed details in the surface and intracellular HER2 distribution that were blurred in the corresponding conventional images, demonstrating the potential of super-resolution microscopy to explore the thus far largely untapped nanoscale regime in tissues stored in biorepositories."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2014"],["dc.identifier.doi","10.1371/journal.pone.0101563"],["dc.identifier.gro","3142087"],["dc.identifier.isi","000339992400018"],["dc.identifier.pmid","25025184"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/10481"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/4400"],["dc.language.iso","en"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.issn","1932-6203"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","STED Super-Resolution Microscopy of Clinical Paraffin-Embedded Human Rectal Cancer Tissue"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Onkologie"],["dc.bibliographiccitation.volume","36"],["dc.contributor.author","Conradi, Lena-Christin"],["dc.contributor.author","Styczen, Hanna"],["dc.contributor.author","Sprenger, Thilo"],["dc.contributor.author","Wolff, Hendrik Andreas"],["dc.contributor.author","Middel, Peter"],["dc.contributor.author","Nagelmeier, I."],["dc.contributor.author","Rüschoff, Josef R."],["dc.contributor.author","Homayounfar, Kia"],["dc.contributor.author","Ghadimi, Michael B."],["dc.contributor.author","Beißbarth, Tim"],["dc.contributor.author","Liersch, Torsten"],["dc.date.accessioned","2018-11-07T09:19:05Z"],["dc.date.available","2018-11-07T09:19:05Z"],["dc.date.issued","2013"],["dc.format.extent","118"],["dc.identifier.isi","000326360900284"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/28551"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Karger"],["dc.publisher.place","Basel"],["dc.relation.issn","1423-0240"],["dc.relation.issn","0378-584X"],["dc.title","HER-2 and HER-3 expression in locally advanced rectal cancer and metachronous metastases: new targets for treatment approaches?"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","26"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Cancer"],["dc.bibliographiccitation.lastpage","35"],["dc.bibliographiccitation.volume","119"],["dc.contributor.author","Sprenger, Thilo"],["dc.contributor.author","Conradi, Lena-Christin"],["dc.contributor.author","Beißbarth, Tim"],["dc.contributor.author","Ermert, Heiko"],["dc.contributor.author","Homayounfar, Kia"],["dc.contributor.author","Middel, Peter"],["dc.contributor.author","Rüschoff, Josef R."],["dc.contributor.author","Wolff, Hendrik Andreas"],["dc.contributor.author","Schueler, Philipp"],["dc.contributor.author","Ghadimi, Michael B."],["dc.contributor.author","Roedel, Claus"],["dc.contributor.author","Becker, Heinz"],["dc.contributor.author","Roedel, Franz"],["dc.contributor.author","Liersch, Torsten"],["dc.date.accessioned","2018-11-07T09:30:52Z"],["dc.date.available","2018-11-07T09:30:52Z"],["dc.date.issued","2013"],["dc.description.abstract","BACKGROUND: The transmembrane glycoprotein CD133 (cluster of differentiation 133; also known as Prominin or PROM1) has been described as a potential stem cell marker in colorectal cancer and is associated with higher tumorigenic potential and resistance to radiochemotherapy (RCT). In this study, CD133 expression was evaluated in pre-RCT tumor biopsies and the corresponding post-RCT surgical specimens from patients with locally advanced rectal adenocarcinoma, and expression levels were correlated with histopathologic features and clinical follow-up. METHODS: One hundred twenty-six patients with International Union Against Cancer (UICC) stage II/III rectal cancer who received preoperative 5-fluorouracil (5-FU)-based RCT within the German Rectal Cancer Trials were investigated. Pre-RCT and post-RCT CD133 expression levels were determined using immunohistochemistry and were correlated with histopathologic parameters, tumor regression grade, cancer recurrence, and patient survival. RESULTS: Compared with pre-RCT biopsies, significantly higher CD133 expression was observed in tumor specimens (P = .01). However, no correlations were observed for either biopsies or tumor specimens between CD133 expression levels, histopathologic characteristics, or survival. In matched analyses of corresponding biopsy/tumor pairs, patients who had an increased fraction of CD133-expressing (CD133+) cells after preoperative RCT had significantly higher residual tumor stages (P = .02) and lower histopathologic tumor regression (P < .01). Moreover, these patients had significantly reduced disease-free survival and cancer-specific overall survival in univariate analysis (P < .001 and P = .004, respectively) and multivariate analysis (P = .003 and P = .024, respectively). CONCLUSIONS: The enrichment of CD133+ cancer cells during preoperative RCT was correlated with minor local tumor response, increased distant cancer recurrence, and decreased survival. The current results indicate that the up-regulation of intratumoral CD133 expression, in contrast to absolute pre-RCT and post-RCT CD133 levels, plays an important role in tumor progression and metastasis in patients with rectal cancer who are receiving neoadjuvant RCT. Cancer 2013. (c) 2012 American Cancer Society."],["dc.description.sponsorship","Deutsche Forschungsgemeinschaft [KFO 179]"],["dc.identifier.doi","10.1002/cncr.27703"],["dc.identifier.isi","000312543000007"],["dc.identifier.pmid","22736392"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/31411"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-blackwell"],["dc.relation.issn","0008-543X"],["dc.title","Enrichment of CD133-expressing cells in rectal cancers treated with preoperative radiochemotherapy is an independent marker for metastasis and survival"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","363"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","Pathology - Research and Practice"],["dc.bibliographiccitation.lastpage","371"],["dc.bibliographiccitation.volume","199"],["dc.contributor.author","Heinmöller, Ernst"],["dc.contributor.author","Bockholt, Anke"],["dc.contributor.author","Werther, Meike"],["dc.contributor.author","Ziemer, Maria"],["dc.contributor.author","Müller, Annegret"],["dc.contributor.author","Ghadimi, B. Michael"],["dc.contributor.author","Rüschoff, Josef"],["dc.date.accessioned","2018-11-07T10:42:50Z"],["dc.date.available","2018-11-07T10:42:50Z"],["dc.date.issued","2003"],["dc.description.abstract","Laser microdissection is considered to be the gold standard of tissue sampling, especially if a defined small tissue area consisting of single or few cells within a heterogeneous tissue compartment is of interest. This sophisticated technique offers the opportunity of rapid and contamination-free tissue sampling for RNA- or DNA-based molecular genetic studies. We have applied laser microdissection to a molecular genetic study of pancreatic intraductal lesions (PanINs) in tissues of chronic pancreatitis, where an exact microdissection of small ducts within a dense fibrous tissue is of paramount importance for following analysis. From nine patients suffering from chronic pancreatitis, formalin-fixed, paraffin-embedded tissue specimens were laser microdissected, and a total of 202 normal ducts and PanINs of grade PanIN-1A to grade PanIN-2 were harvested. After whole genome amplification by improved primer extension and preamplification PCR (I-PEP-PCR), microsatellite-PCR based loss of heterozygosity analysis (LOH) of the tumor suppressor gene loci TP53, p16INK4, and DPC4 was performed. One of 85 informative duct lesions (1.2%) had LOH of TP53, I of 76 duct lesions (1.3%) had LOH of DPC4, and 2/29 duct lesions (6.9%) showed LOH of p16INK4. Microsatellite instability (MSI) was seen in 2 of 178 duct lesions (1.1%). Immunohistochemical staining of p53 protein and DPC4 protein revealed no aberrant expression. These preliminary data indicate that LOH of tumor suppressor genes, important in pancreatic cancer genesis or MSI, can be found in chronic pancreatitis tissues, but their incidence is low."],["dc.identifier.doi","10.1078/0344-0338-00432"],["dc.identifier.isi","000184685600003"],["dc.identifier.pmid","12924436"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/46893"],["dc.language.iso","en"],["dc.notes.status","final"],["dc.notes.submitter","Najko"],["dc.relation.issn","0344-0338"],["dc.title","Laser microdissection of small tissue samples - Application to chronic pancreatitis tissues"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dspace.entity.type","Publication"]]