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Pancreatic Neoplasms: HELP
Articles by Moritz Jesinghaus
Based on 5 articles published since 2010
(Why 5 articles?)
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Between 2010 and 2020, Moritz Jesinghaus wrote the following 5 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 Article Pancreatic neuroendocrine carcinomas reveal a closer relationship to ductal adenocarcinomas than to neuroendocrine tumors G3. 2018

Konukiewitz, Björn / Jesinghaus, Moritz / Steiger, Katja / Schlitter, Anna Melissa / Kasajima, Atsuko / Sipos, Bence / Zamboni, Giuseppe / Weichert, Wilko / Pfarr, Nicole / Klöppel, Günter. ·Institute of Pathology, Technical University of Munich, 81675 Munich, Germany. Electronic address: b.konukiewitz@tum.de. · Institute of Pathology, Technical University of Munich, 81675 Munich, Germany. Electronic address: moritz.jesinghaus@tum.de. · Institute of Pathology, Technical University of Munich, 81675 Munich, Germany. Electronic address: katja.steiger@tum.de. · Institute of Pathology, Technical University of Munich, 81675 Munich, Germany. Electronic address: melissa.schlitter@web.de. · Institute of Pathology, Technical University of Munich, 81675 Munich, Germany. Electronic address: atsuko.kasajima@tum.de. · Institute of Pathology, University Hospital of Tuebingen, 72076 Tuebingen, Germany. Electronic address: Bence.Sipos@med.uni-tuebingen.de. · Institute of Pathology, Sacro Cuore Don Calabria Hospital, 37024 Negrar, Verona, Italy. Electronic address: giuseppe.zamboni@sacrocuore.it. · Institute of Pathology, Technical University of Munich, 81675 Munich, Germany. Electronic address: wilko.weichert@tum.de. · Institute of Pathology, Technical University of Munich, 81675 Munich, Germany. Electronic address: nicole.pfarr@tum.de. · Institute of Pathology, Technical University of Munich, 81675 Munich, Germany. Electronic address: guenter.kloeppel@alumni.uni-kiel.de. ·Hum Pathol · Pubmed #29596894.

ABSTRACT: Pancreatic neuroendocrine carcinoma is a rare aggressive tumor commonly harboring TP53 and RB1 alterations and lacking neuroendocrine-related genetic changes such as mutations in MEN1 and ATRX/DAXX. Little is known about its genetic profile with regard to that of pancreatic ductal adenocarcinoma. We therefore conducted a detailed genetic study in 12 pancreatic neuroendocrine carcinomas of large cell (n = 9) and small cell type (n = 3) using massive parallel sequencing applying a 409-gene panel on an Ion Torrent system. The genetic data were compared with known data of pancreatic ductal adenocarcinoma and correlated with exocrine lineage marker expression. A similar analysis was performed in 11 pancreatic neuroendocrine tumors G3. Neuroendocrine carcinomas harbored 63 somatic mutations in 45 different genes, affecting most commonly TP53 (8/12 cases), KRAS (5/12 cases), and RB1 (loss of expression with or without deletion in 4/12 cases). Five carcinomas had both TP53 and KRAS mutations. Neuroendocrine tumors G3 only shared singular mutations in 5 different genes with neuroendocrine carcinomas, including TP53, CDKN2A, ARID1A, LRP1B, and APC, affecting 5 different cases. Most KRAS-positive neuroendocrine carcinomas also expressed MUC1 (4/5) and carcinoembryonic antigen (3/5) as markers of ductal differentiation. Our data indicate that almost half of the pancreatic neuroendocrine carcinomas are genetically and phenotypically related to pancreatic ductal adenocarcinoma, and might therefore respond to chemotherapies targeting the latter carcinomas.

2 Article Pancreatic Ductal Adenocarcinoma Subtyping Using the Biomarkers Hepatocyte Nuclear Factor-1A and Cytokeratin-81 Correlates with Outcome and Treatment Response. 2018

Muckenhuber, Alexander / Berger, Anne Katrin / Schlitter, Anna Melissa / Steiger, Katja / Konukiewitz, Björn / Trumpp, Andreas / Eils, Roland / Werner, Jens / Friess, Helmut / Esposito, Irene / Klöppel, Günter / Ceyhan, Güralp O / Jesinghaus, Moritz / Denkert, Carsten / Bahra, Marcus / Stenzinger, Albrecht / Sprick, Martin R / Jäger, Dirk / Springfeld, Christoph / Weichert, Wilko. ·Institute of Pathology, Technical University Munich and German Cancer Consortium (DKTK; partner site Munich), Munich, Germany. · Department of Medical Oncology, Heidelberg University Hospital and National Center for Tumor Diseases, Heidelberg, Germany. · Division of Stem Cells and Cancer, German Cancer Research Center (DKFZ) and DKFZ-ZMBH Alliance, Heidelberg, Germany. · Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM GmbH, Heidelberg, Germany. · German Cancer Consortium (DKTK), Heidelberg, Germany. · Division of Theoretical Bioinformatics and Heidelberg Center for Personalised Oncology (DKFZ-HIPO), German Cancer Research Center (DKFZ), Heidelberg, Germany. · Department for Bioinformatics and Functional Genomics, Institute for Pharmacy and Molecular Biotechnology (IPMB) and BioQuant, Heidelberg University, Heidelberg, Germany. · Department of Surgery, University Hospital of the Ludwig-Maximilian University, Munich, Germany. · Department of Surgery, University Hospital of the Technical University Munich, Munich, Germany. · Institute of Pathology, University Hospital Düsseldorf, Düsseldorf, Germany. · Institute of Pathology, Charité University Medicine Berlin and German Cancer Consortium (DKTK; partner site Berlin), Berlin, Germany. · Department of Surgery, Charité University Medicine Berlin, Berlin, Germany. · Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany. · Institute of Pathology, Technical University Munich and German Cancer Consortium (DKTK; partner site Munich), Munich, Germany. wilko.weichert@tum.de. ·Clin Cancer Res · Pubmed #29101303.

ABSTRACT:

3 Article pT but not pN stage of the 8th TNM classification significantly improves prognostication in pancreatic ductal adenocarcinoma. 2017

Schlitter, Anna Melissa / Jesinghaus, Moritz / Jäger, Carsten / Konukiewitz, Björn / Muckenhuber, Alexander / Demir, Ihsan Ekin / Bahra, Marcus / Denkert, Carsten / Friess, Helmut / Kloeppel, Günter / Ceyhan, Güralp O / Weichert, Wilko. ·Institute of Pathology, Technical University Munich, Munich, Germany. Electronic address: melissa.schlitter@tum.de. · Institute of Pathology, Technical University Munich, Munich, Germany; German Cancer Consortium (DKTK), Partner Site Munich, Germany. · Department of Surgery, Klinikum Rechts der Isar, Technical University Munich, Munich, Germany. · Institute of Pathology, Technical University Munich, Munich, Germany. · Department of Surgery, Klinikum Rechts der Isar, Technical University Munich, Munich, Germany; German Cancer Consortium (DKTK), Partner Site Munich, Germany. · Department of Surgery, Charité University Hospital, Berlin, Germany. · Institute of Pathology, Charité University Hospital, Berlin, Germany; German Cancer Consortium (DKTK), Partner Site Berlin, Germany. ·Eur J Cancer · Pubmed #28802189.

ABSTRACT: The UICC TNM (tumour-node-metastasis) staging system for pancreatic ductal adenocarcinoma (PDAC) has been a matter of debate over decades because survival prediction based on T stages was weak and unreliable. To improve staging, the recently published 8th TNM edition (2016) introduced a conceptually completely changed strictly size-based T staging system and a refined N stage for PDAC. To investigate the clinical value of the novel TNM classification, we compared the prognostic impact of pT and pN stage between the 7th and 8th edition in two well-characterised independent German PDAC cohorts from different decades, including a total number of 523 patients. Former UICC T staging (7th edition 2009) resulted in a clustering of pT3 cases (72% and 85% of cases per cohort, respectively) and failed to show significant prognostic differences between the four stages in one of the investigated cohorts (p = 0.074). Application of the novel size-based T stage system resulted in a more equal distribution of cases between the four T categories with a predominance of pT2 tumours (65% and 60% of cases). The novel pT staging algorithm showed greatly improved discriminative power with highly significant overall differences between the four pT stages in both investigated cohorts in univariate and multivariate analyses (p < 0.001, each). In contrast, no prognostic differences were observed between the recently introduced pN1 and pN2 categories in both cohorts (p = 0.970 and p = 0.061). pT stage of resected PDAC patients according to the novel UICC staging protocol (8th edition) significantly improves patient stratification, whereas introduction of an extended N stage protocol does not demonstrate high clinical relevance in our cohorts.

4 Article Somatostatin receptor expression related to TP53 and RB1 alterations in pancreatic and extrapancreatic neuroendocrine neoplasms with a Ki67-index above 20. 2017

Konukiewitz, Björn / Schlitter, Anna Melissa / Jesinghaus, Moritz / Pfister, Dominik / Steiger, Katja / Segler, Angela / Agaimy, Abbas / Sipos, Bence / Zamboni, Giuseppe / Weichert, Wilko / Esposito, Irene / Pfarr, Nicole / Klöppel, Günter. ·Institute of Pathology, Technical University of Munich, Munich, Germany. · Division of Chronic Inflammation and Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany. · Institute of Pathology, Friedrich-Alexander University Erlangen-Nuremberg, University Hospital, Erlangen, Germany. · Institute of Pathology, University Hospital of Tuebingen, Tuebingen, Germany. · Institute of Pathology, Sacro Cuore Hospital of Negrar, Verona, Italy. · Institute of Pathology, Heinrich-Heine-University, Düsseldorf, Germany. ·Mod Pathol · Pubmed #28059098.

ABSTRACT: Somatostatin receptor 2A expression is a feature of well-differentiated neuroendocrine neoplasms and is important for their diagnosis and therapy. Little is known about somatostatin receptor 2A expression in poorly differentiated neuroendocrine neoplasms in relation to TP53 and RB1 status and how these features may contribute to the separation of well from poorly differentiated neuroendocrine neoplasms with a proliferation index above 20%. This study investigates the expression of somatostatin receptors, p53 and Rb1, and TP53 alterations in pancreatic and extrapancreatic well and poorly differentiated neuroendocrine neoplasms (Ki67-index >20%). Thirty-seven poorly differentiated neuroendocrine neoplasms of pancreatic (n=12) and extrapancreatic origin (n=25) as well as 10 well-differentiated neuroendocrine neoplasms of the pancreas (n=9) and rectum (n=1) with a Ki67-index >20% were immunostained for synaptophysin, chromogranin A, Ki67, CD56, p53, Rb1, ATRX, DAXX, progesterone receptor, somatostatin receptor 2A, somatostatin receptor 5, and cytokeratin 20, and sequenced for TP53, exons 5-9. Somatostatin receptor 2A was positive in 6/37 of poorly differentiated and in 8/10 of well-differentiated neuroendocrine neoplasms. One well-differentiated and two poorly differentiated neuroendocrine neoplasms expressed somatostatin receptor 5. Abnormal nuclear p53 and Rb1 staining was found in 29/37 and 22/37 poorly differentiated neuroendocrine neoplasms, respectively, whereas all well-differentiated neuroendocrine neoplasms showed normal p53 and Rb1 expression. TP53 gene alterations were restricted to poorly differentiated neuroendocrine neoplasms (24/34) and correlated well with p53 expression. All cases were progesterone receptor negative. Somatostatin receptor 2A expression is not limited to well-differentiated neuroendocrine neoplasms but also occurs in 16% of poorly differentiated neuroendocrine neoplasms from various sites. Most poorly differentiated neuroendocrine neoplasms are characterized by TP53 alterations and Rb1 loss, usually in the absence of somatostatin receptor 2A expression. In the pancreas, these criteria contribute to separate well-differentiated neuroendocrine neoplasms with a Ki67-index above 20% from poorly differentiated neuroendocrine neoplasms.

5 Article Profiling of cMET and HER Family Receptor Expression in Pancreatic Ductal Adenocarcinomas and Corresponding Lymph Node Metastasis to Assess Relevant Pathways for Targeted Therapies: Looking at the Soil Before Planting the Seed. 2016

Muckenhuber, Alexander / Babitzki, Galina / Thomas, Marlene / Hölzlwimmer, Gabriele / Zajac, Magdalena / Jesinghaus, Moritz / Bergmann, Frank / Werner, Jens / Stenzinger, Albrecht / Weichert, Wilko. ·From the *Institute of Pathology, University Hospital Heidelberg, Ruprecht-Karls Universität, Heidelberg; †Roche Pharma Research and Early Development, Roche Innovation Center, Penzberg, Germany; ‡AstraZeneca, Personalized Healthcare and Biomarkers, Innovative Medicines and Early Development, Cambridge, United Kingdom; §Department of Surgery, University Hospital Grosshadern, Ludwig-Maximilians-Universität, München, Germany; ∥National Center for Tumor Diseases, Heidelberg; and ¶German Cancer Consortium (DKTK), Dresden, Germany. ·Pancreas · Pubmed #26825865.

ABSTRACT: OBJECTIVES: Comprehensive assessment of cMET and HER family receptor tyrosine kinases expression, changes of expression during metastatic progression, amplification status of the MET gene, and correlations with patient characteristics in pancreatic ductal adenocarcinoma (PDAC) was conducted. METHODS: We investigated 56 PDACs and corresponding lymph node metastases for HER1 to HER4 and cMET expression by immunohistochemistry, as well as cMET gene copy numbers by chromogenic in situ hybridization. RESULTS: Of all receptor tyrosine kinases evaluated, cMET expression was highest with 46.5% of tumors showing moderate or strong expression and a weak correlation with gene copy number status (P = 0.04; Spearman ρ = 0.28). cMET expression was increased in metastases. In contrast, expression levels of HER family receptors were generally low both in primaries and metastases. A weak yet significant correlation of HER1 and cMET expression levels was observed (P < 0.001; Spearman ρ = 0.44) and HER1 was often present in poorly differentiated tumors (G3, P = 0.049). CONCLUSIONS: Our data suggest that cMET might constitute an interesting molecule for combining targeted and chemotherapeutic approaches in PDAC, because expression is frequent and increased during metastatic progression. In PDAC, cMET protein expression might be a more useful stratification biomarker than cMET gene amplification, which does not seem to be its primary regulator.