Rüschoff, Josef R.

[["dc.bibliographiccitation.firstpage","9"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Virchows Archiv"],["dc.bibliographiccitation.lastpage","16"],["dc.bibliographiccitation.volume","453"],["dc.contributor.author","Mueller, Annegret"],["dc.contributor.author","Zielinski, Dirk"],["dc.contributor.author","Friedrichs, Nicolaus"],["dc.contributor.author","Oberschmid, Barbara"],["dc.contributor.author","Merkelbach-Bruse, Sabine"],["dc.contributor.author","Schackert, Hans K."],["dc.contributor.author","Linnebacher, Markus"],["dc.contributor.author","Doeberitz, Magnus von Knebel"],["dc.contributor.author","Buettner, Reinhard"],["dc.contributor.author","Rueschoff, Josef"],["dc.date.accessioned","2018-11-07T11:13:50Z"],["dc.date.available","2018-11-07T11:13:50Z"],["dc.date.issued","2008"],["dc.description.abstract","Based on the principle of nonsense-mediated mRNA decay, we sought to identify MLH1 or MSH2-deficient colorectal tumours through relative quantification of mRNA expression with real-time PCR (RT-PCR) analysis. MLH1 and MSH2 mRNAs were almost equally expressed as defined by MLH1 to MSH2 transcript ratio (mean 1.41) in microsatellite stable, mismatch repair (MMR) proficient tumours (n = 16). A close correlation between loss of protein expression and MMR-mRNA levels was found in highly microsatellite instable (MSI-H) tumours deficient of MLH1 or MSH2. MLH1/MSH2 ratio was low in 11 sporadic and nine hereditary MLH1-deficient carcinomas (mean 0.51), whereas the ratio was high in 17 MSH2-deficient hereditary non-polyposis colorectal cancer (HNPCC) associated carcinomas (mean 6.8). Notably, in the normal tissues of HNPCC patients with MSH2 mutations, the MLH1/MSH2 transcript ratios were significantly elevated (ratio > 2.0) as compared to the ratios of normal mucosa in patients with MMR-proficient tumours (27 of 32 ratio < 2.0; p = 0.00113). Analysis of B-lymphocytes of HNPCC patients with proven MMR gene mutation confirmed these findings. In conclusion, RT-PCR allows relative quantification of MMR gene mRNA expression in formalin-fixed and paraffin-embedded tissue. Furthermore, this approach enables quantification of haploinsufficiency due to nonsense-mediated mRNA decay in normal tissue and B-lymphocytes from patients carrying MSH2 germline mutations and may be useful for identification of asymptomatic carriers of pathogenic germline mutations."],["dc.identifier.doi","10.1007/s00428-008-0637-2"],["dc.identifier.isi","000257653300002"],["dc.identifier.pmid","18581137"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/53992"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Springer"],["dc.relation.issn","0945-6317"],["dc.title","Reduced mRNA expression in paraffin-embedded tissue identifies MLH1- and MSH2-deficient colorectal tumours and potential mutation carriers"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["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","3028"],["dc.bibliographiccitation.issue","15_suppl"],["dc.bibliographiccitation.journal","Journal of Clinical Oncology"],["dc.bibliographiccitation.lastpage","3028"],["dc.bibliographiccitation.volume","34"],["dc.contributor.author","Scheel, Andreas H."],["dc.contributor.author","Dietel, Manfred"],["dc.contributor.author","Heukamp, Lukas C."],["dc.contributor.author","Jöhrens, Korinna"],["dc.contributor.author","Kirchner, Thomas"],["dc.contributor.author","Reu, Simone"],["dc.contributor.author","Ruschoff, Josef"],["dc.contributor.author","Schildhaus, Hans-Ulrich"],["dc.contributor.author","Schirmacher, Peter"],["dc.contributor.author","Tiemann, Markus"],["dc.contributor.author","Warth, Arne"],["dc.contributor.author","Weichert, Wilko"],["dc.contributor.author","Fischer, Rieke Nila"],["dc.contributor.author","Wolf, Juergen"],["dc.contributor.author","Buettner, Reinhard"],["dc.date.accessioned","2020-12-10T18:41:30Z"],["dc.date.available","2020-12-10T18:41:30Z"],["dc.date.issued","2016"],["dc.identifier.doi","10.1200/JCO.2016.34.15_suppl.3028"],["dc.identifier.eissn","1527-7755"],["dc.identifier.issn","0732-183X"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/77597"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.title","Diagnostic PD-L1 immunohistochemistry in NSCLC: Results of the first German harmonization study."],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["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","308"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Journal of Molecular Diagnostics"],["dc.bibliographiccitation.lastpage","315"],["dc.bibliographiccitation.volume","6"],["dc.contributor.author","Mueller, A."],["dc.contributor.author","Giuffre, G."],["dc.contributor.author","Edmonston, T. B."],["dc.contributor.author","Mathiak, M."],["dc.contributor.author","Roggendorf, B."],["dc.contributor.author","Heinmoller, E."],["dc.contributor.author","Brodegger, T."],["dc.contributor.author","Tuccari, G."],["dc.contributor.author","Mangold, E."],["dc.contributor.author","Buettner, Reinhardt"],["dc.contributor.author","Ruschoff, J."],["dc.date.accessioned","2018-11-07T10:44:22Z"],["dc.date.available","2018-11-07T10:44:22Z"],["dc.date.issued","2004"],["dc.description.abstract","Hereditary non-polyposis colorectal cancer (HNPCC) accounts for approximately 2 to 4% of the total colorectal cancer burden. For economic reasons a diagnostic \"stepladder\" is recommended. After evaluation of the family history, diagnostic microsatellite instability (MSI) analysis has found its place as a valuable screening tool for HNPCC. Immunohistochemical analysis can help to pinpoint the affected gene. The detection of a mutation in one of the responsible mismatch repair gene confirmed the diagnosis HNPCC. Here we demonstrate our experience of some important pitfalls that will be discussed in this study. In MSI testing, one potential source for false-negative results is intralesional heterogeneity. We demonstrate examples of a flat adenoma and a carcinoma, which required laser microdissection to correctly determine the microsatellite status. In these lesions manual microdissection, the most frequently applied method, was not sufficient. However, the number of cells obtained by using laser microdisssection can fall below a necessary minimum, which can also cause false-negative results of MSI analysis, as shown here in a mucinous carcinoma. In addition, evaluation of immunohistochemically stained tissue slides requires experience to avoid false-positive or false-negative interpretation. A case with two synchronous colorectal cancers revealed loss of MSH2 expression in one carcinoma, whereas the second carcinoma stained positively leading to a false-negative interpretation. In some cases, false-positive results can be obtained, if a perinuclear-staining pattern is interpreted as positive. In summary, there are several potential pitfalls in the molecular screening for HNPCC. Therefore the importance of correct interpretation of clinical data, immunohistochemistry, and microsatellite analysis in combination, performed by a pathologist with experience in molecular genetics is essential. In addition, laser microdissection of tumor areas that have been chosen by a pathologist is highly recommended in cases that cannot be resolved with manual microdissection."],["dc.identifier.doi","10.1016/S1525-1578(10)60526-0"],["dc.identifier.isi","000226190000005"],["dc.identifier.pmid","15507669"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/47252"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Soc Investigative Pathology, Inc"],["dc.relation.issn","1525-1578"],["dc.title","Challenges and pitfalls in HNPCC screening by microsatellite analysis and immunohistochemistry"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","663"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","Virchows Archiv"],["dc.bibliographiccitation.lastpage","672"],["dc.bibliographiccitation.volume","464"],["dc.contributor.author","Rau, Tillman"],["dc.contributor.author","Agaimy, Abbas"],["dc.contributor.author","Gehoff, Anastasia"],["dc.contributor.author","Geppert, Carol"],["dc.contributor.author","Jung, Klaus"],["dc.contributor.author","Knobloch, Katharina"],["dc.contributor.author","Langner, Cord"],["dc.contributor.author","Lugli, Alessandro"],["dc.contributor.author","Groenbus-Lurkin, Irene"],["dc.contributor.author","Nagtegaal, Iris D."],["dc.contributor.author","Rueschoff, Josef"],["dc.contributor.author","Saegert, Xavier"],["dc.contributor.author","Sarbia, Mario"],["dc.contributor.author","Schneider-Stock, Regine"],["dc.contributor.author","Vieth, Michael"],["dc.contributor.author","Zwarthoff, Ellen C."],["dc.contributor.author","Hartmann, Arndt"],["dc.date.accessioned","2018-11-07T09:39:12Z"],["dc.date.available","2018-11-07T09:39:12Z"],["dc.date.issued","2014"],["dc.description.abstract","Criteria for the diagnosis of serrated colorectal lesions (hyperplastic polyp, sessile serrated adenoma without or with dysplasia-which we called mixed polyp-and traditional serrated adenoma) for which consensus has been reached should be validated for applicability in daily practice in terms of inter-observer reproducibility and their association with clinical features and (epi) genetic events. A study set was created from a consecutive series of colorectal polyps (n=1,926) by selecting all sessile serrated adenomas, traditional serrated adenomas and mixed polyps. We added consecutive series of hyperplastic polyps, classical adenomas and normal mucosa samples for a total of 200 specimens. With this series, we conducted an inter-observer study, encompassing ten pathologists with gastrointestinal pathology experience from five European countries, in three rounds in which all cases were microscopically evaluated. An assessment of single morphological criteria was included, and these were correlated with clinical parameters and the mutation status of KRAS, BRAF and PIK3CA and the methylation status of MLH1. Gender, age and localisation were significantly associated with certain types of lesions. Kappa statistics revealed moderate to good interobserver agreement for polyp classification (kappa = 0.56 to 0.63), but for single criteria, this varied considerably (kappa = 0.06 to 0.82). BRAF mutations were frequently found in hyperplastic polyps (86 %, 62/72) and sessile serrated adenomas (80 %, 41/51). KRAS mutations occurred more frequently in traditional serrated adenomas (78%, 7/9) and less so in classical adenomas (20 %, 10/51). Single morphological criteria for sessile serrated"],["dc.identifier.doi","10.1007/s00428-014-1569-7"],["dc.identifier.isi","000338727800005"],["dc.identifier.pmid","24728704"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/33228"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Springer"],["dc.relation.issn","1432-2307"],["dc.relation.issn","0945-6317"],["dc.title","Defined morphological criteria allow reliable diagnosis of colorectal serrated polyps and predict polyp genetics"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","769"],["dc.bibliographiccitation.issue","9"],["dc.bibliographiccitation.journal","Immunotherapy"],["dc.bibliographiccitation.lastpage","782"],["dc.bibliographiccitation.volume","11"],["dc.contributor.author","Schiwitza, Annett"],["dc.contributor.author","Schildhaus, Hans-Ulrich"],["dc.contributor.author","Zwerger, Birgit"],["dc.contributor.author","Rüschoff, Josef"],["dc.contributor.author","Reinhardt, Christian"],["dc.contributor.author","Leha, Andreas"],["dc.contributor.author","Andreas, Stefan"],["dc.contributor.author","Rittmeyer, Achim"],["dc.date.accessioned","2020-12-10T18:43:39Z"],["dc.date.available","2020-12-10T18:43:39Z"],["dc.date.issued","2019"],["dc.identifier.doi","10.2217/imt-2019-0039"],["dc.identifier.eissn","1750-7448"],["dc.identifier.issn","1750-743X"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/78202"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.title","Monitoring efficacy of checkpoint inhibitor therapy in patients with non-small-cell lung cancer"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1630"],["dc.bibliographiccitation.issue","11"],["dc.bibliographiccitation.journal","Modern Pathology"],["dc.bibliographiccitation.lastpage","1644"],["dc.bibliographiccitation.volume","31"],["dc.contributor.author","Koppel, Christina"],["dc.contributor.author","Schwellenbach, Helena"],["dc.contributor.author","Zielinski, Dirk"],["dc.contributor.author","Eckstein, Sina"],["dc.contributor.author","Martin-Ortega, Mercedes"],["dc.contributor.author","D’Arrigo, Corrado"],["dc.contributor.author","Schildhaus, Hans-Ulrich"],["dc.contributor.author","Rüschoff, Josef"],["dc.contributor.author","Jasani, Bharat"],["dc.date.accessioned","2020-12-10T18:09:36Z"],["dc.date.available","2020-12-10T18:09:36Z"],["dc.date.issued","2018"],["dc.identifier.doi","10.1038/s41379-018-0071-1"],["dc.identifier.eissn","1530-0285"],["dc.identifier.issn","0893-3952"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/73702"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.title","Optimization and validation of PD-L1 immunohistochemistry staining protocols using the antibody clone 28-8 on different staining platforms"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","632"],["dc.bibliographiccitation.issue","7"],["dc.bibliographiccitation.journal","International Journal of Colorectal Disease"],["dc.bibliographiccitation.lastpage","641"],["dc.bibliographiccitation.volume","21"],["dc.contributor.author","Mueller, Annegret"],["dc.contributor.author","Beckmann, Carmen"],["dc.contributor.author","Westphal, Gabriela"],["dc.contributor.author","Edmonston, Tina Bocker"],["dc.contributor.author","Friedrichs, Nicolaus"],["dc.contributor.author","Dietmaier, Wolfgang"],["dc.contributor.author","Brasch, Frank E."],["dc.contributor.author","Kloor, Matthias"],["dc.contributor.author","Poremba, Christoph"],["dc.contributor.author","Keller, Gisela"],["dc.contributor.author","Aust, Daniela E."],["dc.contributor.author","Fass, Juergen"],["dc.contributor.author","Buettner, Reinhard"],["dc.contributor.author","Becker, Heinz"],["dc.contributor.author","Rueschoff, Josef"],["dc.date.accessioned","2018-11-07T09:10:51Z"],["dc.date.available","2018-11-07T09:10:51Z"],["dc.date.issued","2006"],["dc.description.abstract","In hereditary nonpolyposis colorectal cancer (HNPCC) syndrome, more than 90% of the carcinomas show microsatellite instability (MSI) due to a loss of mismatch repair (MMR) function. Although adenomas are very common in HNPCC and demonstrate an accelerated adenoma-carcinoma sequence, data about the prevalence and development of MSI in these early neoplastic lesions are lacking. To determine whether MSI and loss of MMR-protein expression are already present in early stages of tumorigenesis and could therefore be used as a screening tool to identify HNPCC patients before they develop an invasive carcinoma, we analyzed 71 adenomas of 36 HNPCC patients during a 5-year follow-up study. These 36 patients were part of a cohort of 122 HNPCC patients who were investigated at the Institute of Pathology, Klinikum Kassel, as part of the multicentric German HNPCC Consortium, which currently serves more than 2,880 registered families. The diagnosis of HNPCC was based either on the detection of a pathogenic germline mutation in the MSH2, MLH1, or MSH6 genes or in cases where a pathogenic mutation was not found; diagnosis of HNPCC was made, because all patients fulfilled the Amsterdam or Bethesda criteria and revealed a high degree of MSI (MSI-H) as well as loss of one of the MMR proteins by IHC in the cancer tissue. We found that most adenomas (58/71) were MSI-H and had loss of MMR-protein expression. Of the 71 adenomas, 3 were MSI-H with expression of all MMR proteins, and 3 out of 71 displayed loss of a MMR protein with the microsatellites being classified as microsatellite stable (MSS). However, 7 of the 31 adenomas that were located more than 5 cm away from the carcinoma revealed an MSS status (n=6) or low in MSI (n=1) and expressed all MMR proteins. In summary, a significant percentage of HNPCC-associated adenomas (7/31, 22.6%) developing at a distance of more than 5 cm from the corresponding carcinoma did not show the MSI-H MMR-deficient phenotype and expressed all MMR genes. To our knowledge, this is the first study that shows that in most HNPCC patients, the mutator pathway is already detectable in adenomas, but MMR-proficient adenomas can also be found. Therefore, screening for MMR deficiency should not be applied routinely in adenomas with the goal to identify HNPCC patients."],["dc.identifier.doi","10.1007/s00384-005-0073-6"],["dc.identifier.isi","000240729200003"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/26590"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Springer"],["dc.relation.issn","0179-1958"],["dc.title","Prevalence of the mismatch-repair-deficient phenotype in colonic adenomas arising in HNPCC patients: results of a 5-year follow-up study"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]