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Author Moritz Jesinghaus

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Morphology Matters: A Critical Reappraisal of the Clinical Relevance of Morphologic Criteria From the 2019 WHO Classification in a Large Colorectal Cancer Cohort Comprising 1004 Cases.

Moritz Jesinghaus, Maxime Schmitt, Corinna Lang, Marianne Reiser, Alexander Scheiter, Björn Konukiewitz, Katja Steiger, Miguel Silva, Markus Tschurtschenthaler, Sebastian Lange, Sebastian Foersch, Karl F Becker, Dieter Saur, Helmut Friess, Kathrin Halfter, Jutta Engel, Melanie Boxberg, Nicole Pfarr, Dirk Wilhelm, Wilko Weichert,

The 2019 World Health Organization (WHO) classification of colorectal carcinoma (CRC) profoundly reclassified CRC subtypes and introduces tumor budding as a second major grading criterion, while condensing conventional grade into a 2-tiered system. So far it remains largely unexplored how these parameters interact with each other and whether they truly ... Read more >>

Am J Surg Pathol (The American journal of surgical pathology)
[2021, 45(7):969-978]

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PALLD mutation in a European family conveys a stromal predisposition for familial pancreatic cancer.

Lucia Liotta, Sebastian Lange, H Carlo Maurer, Kenneth P Olive, Rickmer Braren, Nicole Pfarr, Sebastian Burger, Alexander Muckenhuber, Moritz Jesinghaus, Katja Steiger, Wilko Weichert, Helmut Friess, Roland Schmid, Hana Algül, Philipp J Jost, Juliane Ramser, Christine Fischer, Anne S Quante, Maximilian Reichert, Michael Quante,

BACKGROUNDPancreatic cancer is one of the deadliest cancers, with low long-term survival rates. Despite recent advances in treatment, it is important to identify and screen high-risk individuals for cancer prevention. Familial pancreatic cancer (FPC) accounts for 4%-10% of pancreatic cancers. Several germline mutations are related to an increased risk and ... Read more >>

JCI Insight (JCI insight)
[2021, 6(8):]

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Differential Effects of Trp53 Alterations in Murine Colorectal Cancer.

Alexander M Betzler, Lahiri K Nanduri, Barbara Hissa, Linda Blickensdörfer, Michael H Muders, Janine Roy, Moritz Jesinghaus, Katja Steiger, Wilko Weichert, Matthias Kloor, Barbara Klink, Michael Schroeder, Massimiliano Mazzone, Jürgen Weitz, Christoph Reissfelder, Nuh N Rahbari, Sebastian Schölch,

<h4>Background</h4>Colorectal cancer (CRC) development is a multi-step process resulting in the accumulation of genetic alterations. Despite its high incidence, there are currently no mouse models that accurately recapitulate this process and mimic sporadic CRC. We aimed to develop and characterize a genetically engineered mouse model (GEMM) of Apc/Kras/Trp53 mutant CRC, ... Read more >>

Cancers (Basel) (Cancers)
[2021, 13(4):]

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Sexual Difference Matters: Females with High Microsatellite Instability Show Increased Survival after Neoadjuvant Chemotherapy in Gastric Cancer.

Meike Kohlruss, Katja Ott, Bianca Grosser, Moritz Jesinghaus, Julia Slotta-Huspenina, Alexander Novotny, Alexander Hapfelmeier, Thomas Schmidt, Matthias M Gaida, Wilko Weichert, Gisela Keller,

We aimed to investigate patients with gastric/gastro-esophageal adenocarcinomas for sex- and age-specific differences regarding overall survival (OS) and response to neoadjuvant chemotherapy (CTx) under consideration of tumor specific molecular subtypes. Overall, 717 patients were analyzed, including 426 patients treated with and 291 treated without neoadjuvant CTx. Microsatellite instability (MSI) and ... Read more >>

Cancers (Basel) (Cancers)
[2021, 13(5):]

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Indirect cholinergic activation slows down pancreatic cancer growth and tumor-associated inflammation.

Paulo L Pfitzinger, Laura Fangmann, Kun Wang, Elke Demir, Engin Gürlevik, Bettina Fleischmann-Mundt, Jennifer Brooks, Jan G D'Haese, Steffen Teller, Andreas Hecker, Moritz Jesinghaus, Carsten Jäger, Lei Ren, Rouzanna Istvanffy, Florian Kühnel, Helmut Friess, Güralp Onur Ceyhan, Ihsan Ekin Demir,

<h4>Background</h4>Nerve-cancer interactions are increasingly recognized to be of paramount importance for the emergence and progression of pancreatic cancer (PCa). Here, we investigated the role of indirect cholinergic activation on PCa progression through inhibition of acetylcholinesterase (AChE) via clinically available AChE-inhibitors, i.e. physostigmine and pyridostigmine.<h4>Methods</h4>We applied immunohistochemistry, immunoblotting, MTT-viability, invasion, flow-cytometric-cell-cycle-assays, ... Read more >>

J Exp Clin Cancer Res (Journal of experimental & clinical cancer research : CR)
[2020, 39(1):289]

Cited: 1 time

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Indirect cholinergic activation slows down pancreatic cancer growth and tumor-associated inflammation

Paulo Pfitzinger, Laura Fangmann, Kun Wang, Elke Demir, Engin Gürlevik, Bettina Fleischmann-Mundt, Jennifer Brooks, Jan D'Haese, Steffen Teller, Andreas Hecker, Moritz Jesinghaus, Carsten Jäger, Lei Ren, Rouzanna Istvanffy, Florian Kühnel, Helmut Friess, Güralp Ceyhan, Ihsan Ekin Demir,

<h4>Background: </h4> Nerve-cancer interactions are increasingly recognized to be of paramount importance for the emergence and progression of pancreatic cancer (PCa). Here, we investigated the role of indirect cholinergic activation on PCa progression through inhibition of acetylcholinesterase (AChE) via clinically available AChE-inhibitors, i.e. physostigmine and pyridostigmine. <h4>Methods: </h4>: We applied ... Read more >>

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The immunologic tumor microenvironment in endometrioid endometrial cancer in the morphomolecular context: mutual correlations and prognostic impact depending on molecular alterations.

Barbara Willvonseder, Fabian Stögbauer, Katja Steiger, Moritz Jesinghaus, Peer-Hendrik Kuhn, Christine Brambs, Jutta Engel, Holger Bronger, Georg Philipp Schmidt, Bernhard Haller, Wilko Weichert, Gisela Keller, Aurelia Noske, Nicole Pfarr, Melanie Boxberg,

<h4>Objective</h4>POLE-mutant, microsatellite-instable (MSI), p53-mutant and non-specific molecular profile (NSMP) are TCGA-defined molecular subgroups of endometrial cancer (EC). Hypothesizing that morphology and tumor immunology might differ depending on molecular background concerning composition and prognostic impact, we aimed to comprehensively interconnect morphologic, immunologic and molecular data.<h4>Methods</h4>TCGA-defined molecular groups were determined by immunohistochemistry ... Read more >>

Cancer Immunol Immunother (Cancer immunology, immunotherapy : CII)
[2021, 70(6):1679-1689]

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Pancreatic neuroendocrine tumors with somatostatin expression and paraganglioma-like features.

Björn Konukiewitz, Matthias von Hornstein, Moritz Jesinghaus, Katja Steiger, Wilko Weichert, Sönke Detlefsen, Atsuko Kasajima, Günter Klöppel,

A small fraction of pancreatic neuroendocrine tumors (PanNETs) shows a solid, paraganglioma-like (PG-like) histology. We wanted to know whether these PanNETs have a special hormone expression and are related to paragangliomas (PGs)/pheochromocytomas (PCs). We screened a series of 48 surgically resected PanNETs for their histological growth patterns and their association ... Read more >>

Hum Pathol (Human pathology)
[2020, 102:79-87]

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MCL-1 gains occur with high frequency in lung adenocarcinoma and can be targeted therapeutically.

Enkhtsetseg Munkhbaatar, Michelle Dietzen, Deepti Agrawal, Martina Anton, Moritz Jesinghaus, Melanie Boxberg, Nicole Pfarr, Pidassa Bidola, Sebastian Uhrig, Ulrike Höckendorf, Anna-Lena Meinhardt, Adam Wahida, Irina Heid, Rickmer Braren, Ritu Mishra, Arne Warth, Thomas Muley, Patrina S P Poh, Xin Wang, Stefan Fröhling, Katja Steiger, Julia Slotta-Huspenina, Martijn van Griensven, Franz Pfeiffer, Sebastian Lange, Roland Rad, Magda Spella, Georgios T Stathopoulos, Jürgen Ruland, Florian Bassermann, Wilko Weichert, Andreas Strasser, Caterina Branca, Mathias Heikenwalder, Charles Swanton, Nicholas McGranahan, Philipp J Jost,

Evasion of programmed cell death represents a critical form of oncogene addiction in cancer cells. Understanding the molecular mechanisms underpinning cancer cell survival despite the oncogenic stress could provide a molecular basis for potential therapeutic interventions. Here we explore the role of pro-survival genes in cancer cell integrity during clonal ... Read more >>

Nat Commun (Nature communications)
[2020, 11(1):4527]

Cited: 2 times

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Impact of Tumor Localization and Molecular Subtypes on the Prognostic and Predictive Significance of p53 Expression in Gastric Cancer.

Bianca Grosser, Meike Kohlruss, Julia Slotta-Huspenina, Moritz Jesinghaus, Nicole Pfarr, Katja Steiger, Alexander Novotny, Matthias M Gaida, Thomas Schmidt, Alexander Hapfelmeier, Katja Ott, Wilko Weichert, Gisela Keller,

We investigated the prognostic and predictive impact of p53 expression for gastric cancer (GC) patients treated without or with preoperative chemotherapy (CTx) and its relationship with specific molecular GC subtypes. Specimens from 694 GC patients (562 surgical resection specimens without or after CTx, 132 biopsies before CTx) were analyzed by ... Read more >>

Cancers (Basel) (Cancers)
[2020, 12(6):]

Cited: 2 times

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No increased extracellular volume fraction or conduction time after childhood septal myectomy.

Julia Schleihauf, Julie Cleuziou, Christian Meierhofer, Karin Klingel, Moritz Jesinghaus, Emanuel Kaltenecker, Peter Ewert, Cordula M Wolf,

OBJECTIVES:The aim of this study was to assess the effect of surgical septal myectomy performed during early childhood for severe, drug-refractory hypertrophic cardiomyopathy with left ventricular outflow tract obstruction on the extent of septal myocardial extracellular volume fraction and the potential risk of developing atrioventricular cardiac conduction system disease. METHODS:In ... Read more >>

Eur J Cardiothorac Surg (European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery)
[2020, 57(5):958-964]

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Annexin A1 Expression Capacity as a Determinant for Disease Severity in Crohn's Disease.

Stefan Reischl, Jasmin Troger, Moritz Jesinghaus, Atsuko Kasajima, Dirk Felix Wilhelm, Helmut Friess, Philipp-Alexander Neumann,

INTRODUCTION:Crohn's disease (CD) is characterized by relapsing intestinal inflammation. The anti-inflammatory protein annexin A1 (ANXA1) has been linked to inflammatory processes in the gut. OBJECTIVE:To examine ANXA1 expression patterns in the inflamed intestine of patients with CD and associate ANXA1 expression capacity with disease characteristics. METHODS:Surgical specimens of patients with ... Read more >>

Dig Dis (Digestive diseases (Basel, Switzerland))
[2020, 38(5):398-407]

Cited: 2 times

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IgG4 is Elevated in Eosinophilic Esophagitis but Not in Gastroesophageal Reflux Disease Patients.

Simon Weidlich, Simon Nennstiel, Moritz Jesinghaus, Knut Brockow, Julia Slotta-Huspenina, Monther Bajbouj, Roland M Schmid, Christoph Schlag,

<h4>Background</h4>For eosinophilic esophagitis (EoE) recently an association with immunoglobulin (Ig)G4 rather than IgE has been reported. Gastroesophageal reflux disease (GERD) is the most important differential diagnosis of EoE. We compared esophageal IgG4 plasma cell infiltration and serum IgG4 levels of EoE patients (before and after budesonide therapy) with GERD patients.<h4>Methods</h4>Prospectively ... Read more >>

J Clin Gastroenterol (Journal of clinical gastroenterology)
[2020, 54(1):43-49]

Cited: 2 times

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Pre-operative cellular dissociation grading in biopsies is highly predictive of post-operative tumour stage and patient outcome in head and neck squamous cell carcinoma.

Moritz Jesinghaus, Katja Steiger, Fabian Stögbauer, Bernhard Haller, Andreas Kolk, Ulrich Straßen, Anja Pickhard, Markus Wirth, Miguel Silva, Jan Budczies, Aaron Becker von Rose, Björn Konukiewitz, Peer Kuhn, Konrad Klinghammer, Hendrik Dapper, Stefan Münch, Stephanie E Combs, Wilko Weichert, Melanie Boxberg,

<h4>Background</h4>Pre-operative treatment planning in head and neck squamous cell carcinoma (HNSCC) is mainly dictated by clinical staging, which has major shortcomings. Histologic grading is irrelevant due to its lack of prognostic impact. Recently, a novel grading termed Cellular Dissociation Grade (CDG) based on Tumour Budding and Cell Nest Size was ... Read more >>

Br J Cancer (British journal of cancer)
[2020, 122(6):835-846]

Cited: 1 time

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Post-neoadjuvant cellular dissociation grading based on tumour budding and cell nest size is associated with therapy response and survival in oesophageal squamous cell carcinoma.

Moritz Jesinghaus, Melanie Boxberg, Dirk Wilhelm, Stefan Münch, Hendrik Dapper, Michael Quante, Christoph Schlag, Sebastian Lange, Jan Budczies, Björn Konukiewitz, Martin Mollenhauer, Anna Melissa Schlitter, Karl Friedrich Becker, Marcus Feith, Helmut Friess, Katja Steiger, Stephanie E Combs, Wilko Weichert,

<h4>Background</h4>Cellular Dissociation Grade (CDG) composed of tumour budding and cell nest size has been shown to independently predict prognosis in pre-therapeutic biopsies and primary resections of oesophageal squamous cell carcinoma (ESCC). Here, we aimed to evaluate the prognostic impact of CDG in ESCC after neoadjuvant therapy.<h4>Methods</h4>We evaluated cell nest size ... Read more >>

Br J Cancer (British journal of cancer)
[2019, 121(12):1050-1057]

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Prognostic implication of molecular subtypes and response to neoadjuvant chemotherapy in 760 gastric carcinomas: role of Epstein-Barr virus infection and high- and low-microsatellite instability.

Meike Kohlruss, Bianca Grosser, Marie Krenauer, Julia Slotta-Huspenina, Moritz Jesinghaus, Susanne Blank, Alexander Novotny, Magdalena Reiche, Thomas Schmidt, Liridona Ismani, Alexander Hapfelmeier, Daniel Mathias, Petra Meyer, Matthias M Gaida, Lukas Bauer, Katja Ott, Wilko Weichert, Gisela Keller,

Epstein-Barr virus positivity (EBV(+)) and high-microsatellite instability (MSI-H) have been identified as molecular subgroups in gastric carcinoma. The aim of our study was to determine the prognostic and predictive relevance of these subgroups in the context of platinum/5-fluorouracil (5-FU) based preoperative chemotherapy (CTx). Additionally, we investigated the clinical relevance of ... Read more >>

J Pathol Clin Res (The journal of pathology. Clinical research)
[2019, 5(4):227-239]

Cited: 10 times

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Neoadjuvant versus definitive chemoradiation in patients with squamous cell carcinoma of the esophagus.

Stefan Münch, Steffi U Pigorsch, Michal Devečka, Hendrik Dapper, Marcus Feith, Helmut Friess, Wilko Weichert, Moritz Jesinghaus, Rickmer Braren, Stephanie E Combs, Daniel Habermehl,

<h4>Background</h4>Multimodal treatment with neoadjuvant chemoradiation followed by surgery (nCRT + S) is the treatment of choice for patients with locally advanced or node-positive esophageal squamous cell carcinoma (E-SCC). Those who are unsuitable or who decline surgery can be treated with definitive chemoradiation (dCRT). This study compares the oncologic outcome of ... Read more >>

Radiat Oncol (Radiation oncology (London, England))
[2019, 14(1):66]

Cited: 1 time

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Cellular Dissociation Grading Based on the Parameters Tumor Budding and Cell Nest Size in Pretherapeutic Biopsy Specimens Allows for Prognostic Patient Stratification in Esophageal Squamous Cell Carcinoma Independent From Clinical Staging.

Moritz Jesinghaus, Frido Brühl, Katja Steiger, Peter Klare, Marianne Reiser, Alexander Scheiter, Björn Konukiewitz, Peer Kuhn, Stefan Münch, Michael Quante, Roland M Schmid, Dirk Wilhelm, Markus Feith, Helmut Friess, Stephanie E Combs, Dieter Saur, Melanie Boxberg, Wilko Weichert,

Initial treatment planning in esophageal squamous cell carcinoma mainly relies on clinical staging. Recently, a highly prognostic grading system based on the cellular dissociation parameters Tumor Budding and Cell Nest Size has been proposed for resected esophageal squamous cell carcinoma. To probe for the transferability and relevance of this established ... Read more >>

Am J Surg Pathol (The American journal of surgical pathology)
[2019, 43(5):618-627]

Cited: 6 times

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Tumor Budding and Cell Nest Size Are Highly Prognostic in Laryngeal and Hypopharyngeal Squamous Cell Carcinoma: Further Evidence for a Unified Histopathologic Grading System for Squamous Cell Carcinomas of the Upper Aerodigestive Tract.

Melanie Boxberg, Peer-Hendrik Kuhn, Marianne Reiser, Anna Erb, Katja Steiger, Anja Pickhard, Ulrich Straßen, Isabelle Koob, Andreas Kolk, Arne Warth, Moritz Jesinghaus, Wilko Weichert,

Squamous cell carcinoma (SCC) is the most common cancer of the head and neck region including-among others-laryngeal (LSCC) and hypopharyngeal (HSCC) subsites. LSCC/HSCC are heterogenous diseases with respect to patient outcome. Currently, tumor stage-based patient stratification is essential to predict prognosis and thus selection of the appropriate treatment modalities. In ... Read more >>

Am J Surg Pathol (The American journal of surgical pathology)
[2019, 43(3):303-313]

Cited: 8 times

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Pitfalls in Ga-68-PSMA-PET/CT: incidental finding of parathyroid adenoma.

Christian H Pfob, Ilham Karimov, Moritz Jesinghaus, Alexander Novotny, Wolfgang A Weber, Matthias Eiber, Benedikt Feuerecker,

Eur J Nucl Med Mol Imaging (European journal of nuclear medicine and molecular imaging)
[2019, 46(4):1041]

Cited: 1 time

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Novel prognostic histopathological grading system in oral squamous cell carcinoma based on tumour budding and cell nest size shows high interobserver and intraobserver concordance.

Melanie Boxberg, Christine Bollwein, Korinna Jöhrens, Peer-Hendrik Kuhn, Bernhard Haller, Katja Steiger, Klaus-Dietrich Wolff, Andreas Kolk, Moritz Jesinghaus, Wilko Weichert,

<h4>Aims</h4>Squamous cell carcinoma of the oral cavity (OSCC) is a common tumour entity with a variable, partially highly aggressive clinical course. Recently, we proposed a novel (three-tiered) clinically useful grading scheme strongly associated with patient outcome in OSCC, consisting of a sum score of the histomorphological patterns tumour budding and ... Read more >>

J Clin Pathol (Journal of clinical pathology)
[2019, 72(4):285-294]

Cited: 6 times

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Composition and Clinical Impact of the Immunologic Tumor Microenvironment in Oral Squamous Cell Carcinoma.

Melanie Boxberg, Lena Leising, Katja Steiger, Moritz Jesinghaus, Aezlat Alkhamas, Marion Mielke, Nicole Pfarr, Carolin Götz, Klaus Dietrich Wolff, Wilko Weichert, Andreas Kolk,

Immunotherapy shows promising results and revolutionizes treatment of oral squamous cell carcinoma (OSCC). The immunologic microenvironment might have prognostic/predictive implications. Morphologic immunologic parameters (inflammatory infiltrate, stromal content, and budding activity [BA] [potentially indicating epithelial-mesenchymal transition]) were evaluated in 66 human primary therapy-naive OSCCs. Intraepithelial/stromal tumor-infiltrating lymphocytes (TILs; CD3<sup>+</sup>/CD4<sup>+</sup>/CD8<sup>+</sup>/CD4<sup>+</sup>FOXP3<sup>+</sup>/IL-17A<sup>+</sup>) were quantified, ... Read more >>

J Immunol (Journal of immunology (Baltimore, Md. : 1950))
[2019, 202(1):278-291]

Cited: 11 times

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Immunohistochemical expression of CD44 in oral squamous cell carcinoma in relation to histomorphological parameters and clinicopathological factors.

Melanie Boxberg, Carolin Götz, Selgai Haidari, Christiane Dorfner, Moritz Jesinghaus, Enken Drecoll, Marko Boskov, Klaus D Wolff, Wilko Weichert, Bernhard Haller, Andreas Kolk,

AIMS:Oral squamous cell carcinoma (OSCC) is characterised by its variable clinical course. In addition to the routinely used TNM and Union for International Cancer Control systems, patient-specific prognostic/predictive biomarkers are needed. Promising biomarkers include the determination of the cancer stem cell compartment, which can be identified by CD44 expression (among ... Read more >>

Histopathology (Histopathology)
[2018, 73(4):559-572]

Cited: 5 times

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A microsatellite based multiplex PCR method for the detection of chromosomal instability in gastric cancer.

Meike Kohlruss, Magdalena Reiche, Moritz Jesinghaus, Bianca Grosser, Julia Slotta-Huspenina, Alexander Hapfelmeier, Lukas Bauer, Alexander Novotny, Wilko Weichert, Gisela Keller,

Chromosomal instability (CIN) is a hallmark of distinct subclasses of tumours with potential clinical relevance. The aim of our study was to establish a time and cost effective method for the determination of CIN in gastric carcinomas (GC). We developed a microsatellite based multiplex PCR assay for the detection of ... Read more >>

Sci Rep (Scientific reports)
[2018, 8(1):12551]

Cited: 1 time

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Introducing a novel highly prognostic grading scheme based on tumour budding and cell nest size for squamous cell carcinoma of the uterine cervix.

Moritz Jesinghaus, Johanna Strehl, Melanie Boxberg, Frido Brühl, Adrian Wenzel, Björn Konukiewitz, Anna M Schlitter, Katja Steiger, Arne Warth, Andreas Schnelzer, Marion Kiechle, Matthias W Beckmann, Aurelia Noske, Arndt Hartmann, Grit Mehlhorn, Martin C Koch, Wilko Weichert,

A novel histopathological grading system based on tumour budding and cell nest size has recently been shown to outperform conventional (WHO-based) grading algorithms in several tumour entities such as lung, oral, and oesophageal squamous cell carcinoma (SCC) in terms of prognostic patient stratification. Here, we tested the prognostic value of ... Read more >>

J Pathol Clin Res (The journal of pathology. Clinical research)
[2018, 4(2):93-102]

Cited: 9 times

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