911 results on '"Holger Moch"'
Search Results
152. Supplementary Table 1 from Patterns of Gene Expression and Copy-Number Alterations in von-Hippel Lindau Disease-Associated and Sporadic Clear Cell Carcinoma of the Kidney
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Sabina Signoretti, William G. Kaelin, W. Marston Linehan, Matthew Meyerson, William R. Sellers, Mark A. Rubin, Holger Moch, Robert A. Worrell, David Linhart, Maira M. Pires, Apryle Seeley, Kirsten D. Mertz, Arianna Di Napoli, Jean-Philippe Brunet, and Rameen Beroukhim
- Abstract
Supplementary Table 1 from Patterns of Gene Expression and Copy-Number Alterations in von-Hippel Lindau Disease-Associated and Sporadic Clear Cell Carcinoma of the Kidney
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- 2023
153. Supplementary Figure 4 from Human CD271-Positive Melanoma Stem Cells Associated with Metastasis Establish Tumor Heterogeneity and Long-term Growth
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Lukas Sommer, Maries van den Broek, Reinhard Dummer, Holger Moch, Burkhardt Seifert, Benedetta Belloni, Marie Zipser, Daniela Mihic-Probst, Nikita Kobert, Anne Walter, and Gianluca Civenni
- Abstract
Supplementary Figure 4 from Human CD271-Positive Melanoma Stem Cells Associated with Metastasis Establish Tumor Heterogeneity and Long-term Growth
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- 2023
154. Supplementary Methods from Patterns of Gene Expression and Copy-Number Alterations in von-Hippel Lindau Disease-Associated and Sporadic Clear Cell Carcinoma of the Kidney
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Sabina Signoretti, William G. Kaelin, W. Marston Linehan, Matthew Meyerson, William R. Sellers, Mark A. Rubin, Holger Moch, Robert A. Worrell, David Linhart, Maira M. Pires, Apryle Seeley, Kirsten D. Mertz, Arianna Di Napoli, Jean-Philippe Brunet, and Rameen Beroukhim
- Abstract
Supplementary Methods from Patterns of Gene Expression and Copy-Number Alterations in von-Hippel Lindau Disease-Associated and Sporadic Clear Cell Carcinoma of the Kidney
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- 2023
155. Supplementary Table 2 from Patterns of Gene Expression and Copy-Number Alterations in von-Hippel Lindau Disease-Associated and Sporadic Clear Cell Carcinoma of the Kidney
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Sabina Signoretti, William G. Kaelin, W. Marston Linehan, Matthew Meyerson, William R. Sellers, Mark A. Rubin, Holger Moch, Robert A. Worrell, David Linhart, Maira M. Pires, Apryle Seeley, Kirsten D. Mertz, Arianna Di Napoli, Jean-Philippe Brunet, and Rameen Beroukhim
- Abstract
Supplementary Table 2 from Patterns of Gene Expression and Copy-Number Alterations in von-Hippel Lindau Disease-Associated and Sporadic Clear Cell Carcinoma of the Kidney
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- 2023
156. Supplementary Figures 1 - 6 from Tumor Suppressor VHL Functions in the Control of Mitotic Fidelity
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Wilhelm Krek, Holger Moch, Thomas C. Weber, Maria Duda, and Michael P. Hell
- Abstract
PDF file - 515K, Supplemental Figure 1: Reintroduction of full-length pVHL rescues mitotic defects in Vhl-negative MREC cells. Supplemental Figure 2: Further characterization of kidney injury surgery. Supplemental Figure 3: Characterization of Vhl Knockout Status and proliferation and apoptosis rate in Kidneys. Supplemental Figure 4: Characterization of the spindle angle determination and discrimination of proximal and distal kidney tubules. Supplemental Figure 5: Scoring system of chromosome missegregation errors. Supplemental Figure 6: Assessment of proliferation and apoptotic response in kidneys 4 months post ischemic injury.
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- 2023
157. Supplementary Figure 5 from Human CD271-Positive Melanoma Stem Cells Associated with Metastasis Establish Tumor Heterogeneity and Long-term Growth
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Lukas Sommer, Maries van den Broek, Reinhard Dummer, Holger Moch, Burkhardt Seifert, Benedetta Belloni, Marie Zipser, Daniela Mihic-Probst, Nikita Kobert, Anne Walter, and Gianluca Civenni
- Abstract
Supplementary Figure 5 from Human CD271-Positive Melanoma Stem Cells Associated with Metastasis Establish Tumor Heterogeneity and Long-term Growth
- Published
- 2023
158. Supplementary Figure 2 from Human CD271-Positive Melanoma Stem Cells Associated with Metastasis Establish Tumor Heterogeneity and Long-term Growth
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Lukas Sommer, Maries van den Broek, Reinhard Dummer, Holger Moch, Burkhardt Seifert, Benedetta Belloni, Marie Zipser, Daniela Mihic-Probst, Nikita Kobert, Anne Walter, and Gianluca Civenni
- Abstract
Supplementary Figure 2 from Human CD271-Positive Melanoma Stem Cells Associated with Metastasis Establish Tumor Heterogeneity and Long-term Growth
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- 2023
159. Utility of BAP1, p16 and MTAP immunohistochemistry in cytological and histological samples of pleural mesotheliomas
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Vera Amacher, Peter Karl Bode, Holger Moch, Daniela Lenggenhager, and Bart Vrugt
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Histology ,General Medicine ,Pathology and Forensic Medicine - Abstract
Introduction: In most cases the diagnostic workup of pleural mesotheliomas (MPM) starts with cytological examination of pleural effusion, but histology is needed to confirm the diagnosis. The introduction of BAP1 and MTAP immunohistochemistry have become a powerful tool to confirm the malignant nature of mesothelial proliferations also in cytological specimens. The objective of this study is to determine the concordance of BAP1, MTAP and p16 expression between cytological and histological samples of patients with MPM. Methods: Immunohistochemistry of BAP1, MTAP and p16 was performed on cytological samples and compared with the corresponding histological specimen of 25 patients with MPM. Inflammatory and stromal cells served as positive internal control for all three markers. In addition, samples of 11 patients with reactive mesothelial proliferations served as an external control group. Results: Loss of BAP1, MTAP and p16 expression was found in 68%, 72% and 92% of MPM, respectively. Loss of MTAP was associated with loss of p16 expression in all cases. Concordance of BAP1 between cytological and corresponding histological samples was 100% (kappa coefficient 1; p = 0.008). For MTAP and p16 kappa coefficient was 0.9 (p = 0.01) and 0.8 (p = 0.7788), respectively. Conclusions: Concordant BAP1, MTAP and p16 expression is found between cytological and corresponding histological samples, indicating that a reliable diagnosis of MPM can be made on cytology only. Of the three markers BAP1 and MTAP are most reliable in distinguishing malignant from reactive mesothelial proliferations
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- 2023
160. Ex Vivo Drug Testing in Patient-derived Papillary Renal Cancer Cells Reveals EGFR and the BCL2 Family as Therapeutic Targets
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Silvia Angori, Amir Banaei-Esfahani, Katharina Mühlbauer, Hella A. Bolck, Abdullah Kahraman, Tülay Karakulak, Cédric Poyet, Michaela Feodoroff, Swapnil Potdar, Olli Kallioniemi, Vilja Pietiäinen, Peter Schraml, and Holger Moch
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Urology - Published
- 2023
161. Prostate Adenocarcinoma Grade Group 1: Rationale for Retaining a Cancer Label in the 2022 World Health Organization Classification
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George J. Netto, Mahul B. Amin, Eva M. Compérat, Anthony J. Gill, Arndt Hartmann, Holger Moch, Santosh Menon, Maria R. Raspollini, Mark A. Rubin, John R. Srigley, Puay Hoon Tan, Satish K. Tickoo, Toyonori Tsuzuki, Samra Turajlic, Ian Cree, Daniel M. Berney, University of Zurich, and Netto, George J
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2748 Urology ,Urology ,10049 Institute of Pathology and Molecular Pathology ,610 Medicine & health - Abstract
We present the rationale for keeping the "cancer" label for grade group 1 (GG1) prostate cancer. Maintaining GG1 as the lowest grade outweighs the potential benefits that a benign designation may bring. Patient and surgeon education on the vital role of active surveillance for GG1 cancers and avoidance of overtreatment should be the focus rather than such a drastic change in nomenclature.
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- 2023
- Full Text
- View/download PDF
162. CanIsoNet: a database to study the functional impact of isoform switching events in diseases
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Tülay Karakulak, Damian Szklarczyk, Cemil Can Saylan, Holger Moch, Christian von Mering, and Abdullah Kahraman
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General Medicine - Abstract
Motivation Alternative splicing, as an essential regulatory mechanism in normal mammalian cells, is frequently disturbed in cancer and other diseases. Switches in the expression of most dominant alternative isoforms can alter protein interaction networks of associated genes giving rise to disease and disease progression. Here, we present CanIsoNet, a database to view, browse and search isoform switching events in diseases. CanIsoNet is the first webserver that incorporates isoform expression data with STRING interaction networks and ClinVar annotations to predict the pathogenic impact of isoform switching events in various diseases. Results Data in CanIsoNet can be browsed by disease or searched by genes or isoforms in annotation-rich data tables. Various annotations for 11 811 isoforms and 14 357 unique isoform switching events across 31 different disease types are available. The network density score for each disease-specific isoform, PFAM domain IDs of disrupted interactions, domain structure visualization of transcripts and expression data of switched isoforms for each sample is given. Additionally, the genes annotated in ClinVar are highlighted in interactive interaction networks. Availability and implementation CanIsoNet is freely available at https://www.caniso.net. The source codes can be found under a Creative Common License at https://github.com/kahramanlab/CanIsoNet_Web. Supplementary information Supplementary data are available at Bioinformatics Advances online.
- Published
- 2023
163. Männliche Geschlechtsorgane und ableitende Harnwege
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Daniel Eberli, Holger Moch, Thomas Cerny, and Kirill Karlin
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- 2023
164. Vaccination with designed neopeptides induces intratumoral, cross-reactive CD4+ T cell responses in glioblastoma
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Jian Wang, Tobias Weiss, Marian C. Neidert, Nora C. Toussaint, Reza Naghavian, Carla Sellés Moreno, Magdalena Foege, Paula Tomas Ojer, Gioele Medici, Ivan Jelcic, Daniel Schulz, Elisabeth Rushing, Susanne Dettwiler, Barbara Schrörs, Joo Heon Shin, Ron McKay, Catherine J. Wu, Andreas Lutterotti, Mireia Sospedra, Holger Moch, Erich F. Greiner, Bernd Bodenmiller, Luca Regli, Michael Weller, Patrick Roth, Roland Martin, and University of Zurich
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Cancer Research ,Oncology ,10049 Institute of Pathology and Molecular Pathology ,610 Medicine & health ,11493 Department of Quantitative Biomedicine ,10040 Clinic for Neurology - Abstract
Purpose: The low mutational load of some cancers is considered one reason for the difficulty to develop effective tumor vaccines. To overcome this problem, we developed a strategy to design neopeptides through single amino acid mutations to enhance their immunogenicity. Experimental Design: Exome and RNA sequencing as well as in silico HLA-binding predictions to autologous HLA molecules were used to identify candidate neopeptides. Subsequently, in silico HLA-anchor placements were used to deduce putative T-cell receptor (TCR) contacts of peptides. Single amino acids of TCR contacting residues were then mutated by amino acid replacements. Overall, 175 peptides were synthesized and sets of 25 each containing both peptides designed to bind to HLA class I and II molecules applied in the vaccination. Upon development of a tumor recurrence, the tumor-infiltrating lymphocytes (TIL) were characterized in detail both at the bulk and clonal level. Results: The immune response of peripheral blood T cells to vaccine peptides, including natural peptides and designed neopeptides, gradually increased with repetitive vaccination, but remained low. In contrast, at the time of tumor recurrence, CD8+ TILs and CD4+ TILs responded to 45% and 100%, respectively, of the vaccine peptides. Furthermore, TIL-derived CD4+ T-cell clones showed strong responses and tumor cell lysis not only against the designed neopeptide but also against the unmutated natural peptides of the tumor. Conclusions: Turning tumor self-peptides into foreign antigens by introduction of designed mutations is a promising strategy to induce strong intratumoral CD4+ T-cell responses in a cold tumor like glioblastoma., Clinical Cancer Research, 28 (24), ISSN:1078-0432, ISSN:1557-3265
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- 2022
165. ROS1 genomic rearrangements are rare actionable drivers in microsatellite stable colorectal cancer
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Dilara Akhoundova, Saskia Hussung, Smruthy Sivakumar, Antonia Töpfer, Markus Rechsteiner, Abdullah Kahraman, Fabian Arnold, Florian Angst, Christian Britschgi, Martin Zoche, Holger Moch, Achim Weber, Ethan Sokol, Ralph M. Fritsch, University of Zurich, and Fritsch, Ralph M
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Proto-Oncogene Proteins B-raf ,Gene Rearrangement ,Cancer Research ,Lung Neoplasms ,610 Medicine & health ,Genomics ,Protein-Tyrosine Kinases ,Protein Serine-Threonine Kinases ,Proto-Oncogene Proteins p21(ras) ,Crizotinib ,Oncology ,Proto-Oncogene Proteins ,10049 Institute of Pathology and Molecular Pathology ,10032 Clinic for Oncology and Hematology ,Humans ,2730 Oncology ,1306 Cancer Research ,Reactive Oxygen Species ,Colorectal Neoplasms ,Microsatellite Repeats - Abstract
c-Ros oncogene 1, receptor tyrosine kinase (ROS1) genomic rearrangements have been reported previously in rare cases of colorectal cancer (CRC), yet little is known about the frequency, molecular characteristics, and therapeutic vulnerabilities of ROS1-driven CRC. We analyzed a clinical dataset of 40 589 patients with CRC for ROS1 genomic rearrangements and their associated genomic characteristics (Foundation Medicine, Inc [FMI]). We moreover report the disease course and treatment response of an index patient with ROS1-rearranged metastatic CRC. ROS1 genomic rearrangements were identified in 34 (0.08%) CRC samples. GOPC-ROS1 was the most common ROS1 fusion identified (11 samples), followed by TTC28-ROS1 (3 samples). Four novel 5' gene partners of ROS1 were identified (MCM9, SRPK1, EPHA6, P4HA1). Contrary to previous reports on fusion-positive CRC, ROS1-rearrangements were found exclusively in microsatellite stable (MSS) CRCs. KRAS mutations were significantly less abundant in ROS1-rearranged vs ROS1 wild type cases. The index patient presented with chemotherapy-refractory metastatic right-sided colon cancer harboring GOPC-ROS1. Molecularly targeted treatment with crizotinib induced a rapid and sustained partial response. After 15 months on crizotinib disseminated tumor progression occurred and KRAS Q61H emerged in tissue and liquid biopsies. ROS1 rearrangements define a small, yet therapeutically actionable molecular subgroup of MSS CRC. In summary, the high prevalence of GOPC-ROS1 and noncanonical ROS1 fusions pose diagnostic challenges. We advocate NGS-based comprehensive molecular profiling of MSS CRCs that are wild type for RAS and BRAF and patient enrollment in precision trials.
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- 2022
166. Onkozytäre Tumoren der Niere – neue Differenzialdiagnosen
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I. Polifka, Riuko Ohashi, Holger Moch, and University of Zurich
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Gynecology ,medicine.medical_specialty ,business.industry ,10049 Institute of Pathology and Molecular Pathology ,medicine ,610 Medicine & health ,business ,Pathology and Forensic Medicine - Abstract
Das Spektrum der onkozytaren Tumoren der Niere hat sich durch neue Erkenntnisse erweitert. Erstellung einer Ubersicht zur Differenzialdiagnose onkozytarer Tumoren der Niere. Eine Literaturrecherche zu onkozytaren Tumoren der Niere wurde durchgefuhrt und die etablierten Entitaten werden dargestellt. Mogliche Differenzialdiagnosen werden diskutiert. Neben den bereits anerkannten Entitaten der World Health Organisation (WHO) 2016 gibt es neue Erkenntnisse in der Gruppe der bisher nicht eindeutig klassifizierbaren onkozytaren Nierentumoren, bei denen sich Charakteristika in Immunhistochemie und auf molekularer Ebene abzeichnen, die zukunftig eine Etablierung neuer Entitaten anbahnen. Wichtige Differenzialdiagnosen konnen zudem abgegrenzt werden, was eine spezifische Therapie onkozytarer Nierentumoren ermoglicht. Die korrekte Diagnose onkozytarer Nierentumoren ermoglicht nicht nur eine verbesserte Prognoseeinschatzung (und ggf. spezifische Therapieoptionen), sondern ist auch im Hinblick auf eine mogliche Assoziation zu einem Tumordispositionssyndrom klinisch von Bedeutung.
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- 2021
167. The 2022 World Health Organization Classification of Tumours of the Urinary System and Male Genital Organs-Part A: Renal, Penile, and Testicular Tumours
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Holger Moch, Mahul B. Amin, Daniel M. Berney, Eva M. Compérat, Anthony J. Gill, Arndt Hartmann, Santosh Menon, Maria R. Raspollini, Mark A. Rubin, John R. Srigley, Puay Hoon Tan, Satish K. Tickoo, Toyonori Tsuzuki, Samra Turajlic, Ian Cree, George J. Netto, University of Zurich, and Moch, Holger
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Male ,2748 Urology ,Urology ,Papillomavirus Infections ,Genome Integrity & Repair ,Neuroectodermal Tumors ,Receptor Protein-Tyrosine Kinases ,610 Medicine & health ,Genitalia, Male ,Neoplasms, Germ Cell and Embryonal ,Tumour Biology ,World Health Organization ,Kidney Neoplasms ,Signalling & Oncogenes ,Testicular Neoplasms ,10049 Institute of Pathology and Molecular Pathology ,Humans ,Carcinoma, Renal Cell ,Genetics & Genomics ,Computational & Systems Biology - Abstract
The fifth edition of the World Health Organization (WHO) classification of urogenital tumours (WHO "Blue Book"), published in 2022, contains significant revisions. This review summarises the most relevant changes for renal, penile, and testicular tumours. In keeping with other volumes in the fifth edition series, the WHO classification of urogenital tumours follows a hierarchical classification and lists tumours by site, category, family, and type. The section "essential and desirable diagnostic criteria" included in the WHO fifth edition represents morphologic diagnostic criteria, combined with immunohistochemistry and relevant molecular tests. The global introduction of massive parallel sequencing will result in a diagnostic shift from morphology to molecular analyses. Therefore, a molecular-driven renal tumour classification has been introduced, taking recent discoveries in renal tumour genomics into account. Such novel molecularly defined epithelial renal tumours include SMARCB1-deficient medullary renal cell carcinoma (RCC), TFEB-altered RCC, Alk-rearranged RCC, and ELOC-mutated RCC. Eosinophilic solid and cystic RCC is a novel morphologically defined RCC entity. The diverse morphologic patterns of penile squamous cell carcinomas are grouped as human papillomavirus (HPV) associated and HPV independent, and there is an attempt to simplify the morphologic classification. A new chapter with tumours of the scrotum has been introduced. The main nomenclature of testicular tumours is retained, including the use of the term "germ cell neoplasia in situ" (GCNIS) for the preneoplastic lesion of most germ cell tumours and division from those not derived from GCNIS. Nomenclature changes include replacement of the term "primitive neuroectodermal tumour" by "embryonic neuroectodermal tumour" to separate these tumours clearly from Ewing sarcoma. The term "carcinoid" has been changed to "neuroendocrine tumour", with most examples in the testis now classified as "prepubertal type testicular neuroendocrine tumour".
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- 2022
168. A systematic comparison of pan-Trk immunohistochemistry assays across multiple cancer types
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Martina Haberecker, Antonia Töpfer, Francesca Malega, Holger Moch, and Chantal Pauli
- Abstract
NTRK-rearranged tumors are rare but can be successfully treated using anti-TRK–targeted therapies making NTRK testing important for treatment choices in patients with advanced cancers. Pan-Trk immunohistochemistry (IHC) has become a valuable and affordable screening tool, but the choice of antibodies and IHC protocols to investigate biomarkers is not standardized. As NTRK fusion-positive tumors are rare, systematic technical studies are sparse. Pan-Trk IHC has been reported as a fast technique for the identification of NTRK fusion driven tumors, with a reported sensitivity of about 85–90% with differences depending on which NTRK gene is involved. Furthermore, antibody specificity seems to be dependent on tumor type. In this work, we studied the intermethod agreement for four pan-Trk IHC methods, using three different clones: EPR17341 (Abcam and Ventana), EP1058Y (Abcam), A7H6R (Cell Signaling) in 18 molecularly confirmed NTRK-rearranged tumors. We further included NTRK mutated (n = 8) and amplified (N = 15) tumors as well as NTRK wild type tumors driven by other gene fusions such as ALK, ROS1 and BCOR (n = 20) and salivary gland tumors (n = 16). Among 77 tumors, pan-Trk IHC was classified as positive using an H score ≥ 5. The overall sensitivity and specificity to separate NTRK-rearranged tumors from NTRK fusion-negative tumors was 100% and 73.8%, respectively, for clone EPR17341 using an in house and the Ventana protocol. For clone A7H6R (in house protocol) we had 93.8% sensitivity and 80.3% specificity and clone EP1058Y (in house protocol) showed 73.3% sensitivity and 32.8% specificity. EPR17341 (both protocols) and A7H6R clones showed also a good interrater agreement in terms of H-score (κ = from 0.936 to 0.956) but only a moderate agreement against the reference assay (molecular data) considering positive and negative results (κ = from 0.593 to 0.591). We identified clones and assays/protocol that can be reliably used by pathologist for the screening of NTRK rearranged tumors.
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- 2022
169. Expert opinion on NSCLC small specimen biomarker testing — Part 2: Analysis, reporting, and quality assessment
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Frédérique Penault-Llorca, Keith M. Kerr, Pilar Garrido, Erik Thunnissen, Elisabeth Dequeker, Nicola Normanno, Simon J. Patton, Jenni Fairley, Joshua Kapp, Daniëlle de Ridder, Aleš Ryška, Holger Moch, Breast Cancer Translational Research Laboratory, Institut Jules Bordet [Bruxelles], Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB)-Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Translational Cancer Research Unit [Antwerp], Charité, Institute of Pathology, Translational Tumorpathology Unit, Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA), Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER, Division of Pathology and Laboratory Medicine, Università degli Studi di Milano = University of Milan (UNIMI)-European Institute of Oncology [Milan] (ESMO), University of the Sunshine Coast (USC), Erasmus University Medical Center [Rotterdam] (Erasmus MC), University of Zurich, and Moch, Holger
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MESH: Expert Testimony ,Lung Neoplasms ,MESH: Mutation ,CELL LUNG-CANCER ,610 Medicine & health ,Best practice ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,MOLECULAR-PATHOLOGY ,RECOMMENDATIONS ,Pathology and Forensic Medicine ,Non-small cell lung carcinoma ,1307 Cell Biology ,Breast cancer ,Carcinoma, Non-Small-Cell Lung ,10049 Institute of Pathology and Molecular Pathology ,RET FUSIONS ,Pathology ,1312 Molecular Biology ,Molecular diagnostics ,Humans ,Expert Testimony ,Molecular Biology ,MESH: High-Throughput Nucleotide Sequencing ,OUTCOMES ,Science & Technology ,MESH: Humans ,Liquid biopsy ,High-Throughput Nucleotide Sequencing ,Cell Biology ,General Medicine ,MUTATION STATUS ,DNA ,Biomarker ,IN-SITU HYBRIDIZATION ,ONCOLOGY ,Immunohistochemistry ,External quality assessment ,MESH: Lung Neoplasms ,2734 Pathology and Forensic Medicine ,MESH: Reproducibility of Results ,Mutation ,Trastuzumab-deruxtecan ,Next-generation sequencing ,MESH: Biomarkers ,HER2-low ,Life Sciences & Biomedicine ,Biomarkers ,MESH: Carcinoma, Non-Small-Cell Lung - Abstract
The diagnostic work-up for non-small cell lung cancer (NSCLC) requires biomarker testing to guide therapy choices. This article is the second of a two-part series. In Part 1, we summarised evidence-based recommendations for obtaining and processing small specimen samples (i.e. pre-analytical steps) from patients with advanced NSCLC. Here, in Part 2, we summarise evidence-based recommendations relating to analytical steps of biomarker testing (and associated reporting and quality assessment) of small specimen samples in NSCLC. As the number of biomarkers for actionable (genetic) targets and approved targeted therapies continues to increase, simultaneous testing of multiple actionable oncogenic drivers using next-generation sequencing (NGS) becomes imperative, as set forth in European Society for Medical Oncology guidelines. This is particularly relevant in advanced NSCLC, where tissue specimens are typically limited and NGS may help avoid tissue exhaustion compared with sequential biomarker testing. Despite guideline recommendations, significant discrepancies in access to NGS persist across Europe, primarily due to reimbursement constraints. The use of increasingly complex testing methods also has implications for the reporting of results. Molecular testing reports should include clinical interpretation with additional commentary on sample adequacy as appropriate. Molecular tumour boards are recommended to facilitate the interpretation of complex genetic information arising from NGS, and to collaboratively determine the optimal treatment for patients with NSCLC. Finally, whichever testing modality is employed, it is essential that adequate internal and external validation and quality control measures are implemented. ispartof: VIRCHOWS ARCHIV vol:481 issue:3 pages:351-366 ispartof: location:Germany status: published
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- 2022
170. Biallelic ELOC-Inactivated Renal Cell Carcinoma: Molecular Features Supporting Classification as a Distinct Entity
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Aashil A. Batavia, Dorothea Rutishauser, Bettina Sobottka, Peter Schraml, Niko Beerenwinkel, and Holger Moch
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Pathology and Forensic Medicine - Published
- 2023
171. Randomized Tree Ensembles for Object Detection in Computational Pathology.
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Thomas J. Fuchs, Johannes Haybaeck, Peter J. Wild, Mathias Heikenwalder, Holger Moch, Adriano Aguzzi, and Joachim M. Buhmann
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- 2009
- Full Text
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172. Graph-Based Pancreatic Islet Segmentation for Early Type 2 Diabetes Mellitus on Histopathological Tissue.
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Xenofon E. Floros, Thomas J. Fuchs, Markus P. Rechsteiner, Giatgen Spinas, Holger Moch, and Joachim M. Buhmann
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- 2009
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173. Weakly Supervised Cell Nuclei Detection and Segmentation on Tissue Microarrays of Renal Clear Cell Carcinoma.
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Thomas J. Fuchs, Tilman Lange, Peter J. Wild, Holger Moch, and Joachim M. Buhmann
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- 2008
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174. Computational Pathology Analysis of Tissue Microarrays Predicts Survival of Renal Clear Cell Carcinoma Patients.
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Thomas J. Fuchs, Peter J. Wild, Holger Moch, and Joachim M. Buhmann
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- 2008
- Full Text
- View/download PDF
175. What’s behind 68Ga-PSMA-11 uptake in primary prostate cancer PET? Investigation of histopathological parameters and immunohistochemical PSMA expression patterns
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Niels J. Rupp, Irene A. Burger, Riccardo Laudicella, Daniela A. Ferraro, Jan H. Rüschoff, Holger Moch, Thomas Hermanns, Urs J. Muehlematter, Ann-Katrin Rodewald, and Daniel Eberli
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Pathology ,medicine.medical_specialty ,medicine.diagnostic_test ,business.industry ,Prostatectomy ,medicine.medical_treatment ,General Medicine ,urologic and male genital diseases ,medicine.disease ,Prostate cancer ,Positron emission tomography ,Infiltrative Growth Pattern ,Biopsy ,medicine ,Glutamate carboxypeptidase II ,Biomarker (medicine) ,Immunohistochemistry ,Radiology, Nuclear Medicine and imaging ,business - Abstract
Purpose Prostate-specific membrane antigen (PSMA-) PET has become a promising tool in staging and restaging of prostate carcinoma (PCa). However, specific primary tumour features might impact accuracy of PSMA-PET for PCa detection. We investigated histopathological parameters and immunohistochemical PSMA expression patterns on radical prostatectomy (RPE) specimens and correlated them to the corresponding 68Ga-PSMA-11-PET examinations. Methods RPE specimens of 62 patients with preoperative 68Ga-PSMA-11-PET between 2016 and 2018 were analysed. WHO/ISUP grade groups, growth pattern (expansive vs. infiltrative), tumour area and diameter as well as immunohistochemical PSMA heterogeneity, intensity and negative tumour area (PSMA%neg) were correlated with spatially corresponding SUVmax on 68Ga-PSMA-11-PET in a multidisciplinary analysis. Results All tumours showed medium to strong membranous (2–3 +) and weak to strong cytoplasmic (1–3 +) PSMA expression. Heterogeneously expressed PSMA was found in 38 cases (61%). Twenty-five cases (40%) showed at least 5% and up to 80% PSMA%neg. PSMA%neg, infiltrative growth pattern, smaller tumour area and diameter and WHO/ISUP grade group 2 significantly correlated with lower SUVmax values. A ROC curve analysis revealed 20% PSMA%neg as an optimal cutoff with the highest sensitivity and specificity (89% and 86%, AUC 0.923) for a negative PSMA-PET scan. A multiple logistic regression model revealed tumoural PSMA%neg (p p = 0.0497, OR = 306.537) as significant predictors for a negative PSMA-PET scan. Conclusions We describe PSMA%neg, infiltrative growth pattern, smaller tumour size and WHO/ISUP grade group 2 as parameters associated with a lower 68Ga-PSMA-11 uptake in prostate cancer. These findings can serve as fundament for future biopsy-based biomarker development to enable an individualized, tumour-adapted imaging approach.
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- 2021
176. What's new in WHO fifth edition - urinary tract
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Eva Compérat, Mahul B Amin, Dan M Berney, Ian Cree, Santosh Menon, Holger Moch, George J Netto, Vishal Rao, Maria Rosaria Raspollini, Mark A Rubin, John R Srigley, Puay Hoon Tan, Satish Kumar Tickoo, Samra Turajlic, and Toyonori Tsuzuki
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Urologic Neoplasms ,Histology ,Urinary Bladder Neoplasms ,Humans ,General Medicine ,Urinary Tract ,World Health Organization ,Pathology and Forensic Medicine - Abstract
The fifth edition of the WHO Blue Book on urological tumours, specifically in the bladder chapter, represents a refinement and update in the classification of bladder tumours building on the aggregate major changes made in previous editions. Progress in the molecular underpinnings of urothelial tumours, particularly with promising stratifiers for more precision-based treatment approaches, have been made. Special attention has been paid to burning questions in bladder pathology, such as grading, heterogeneous lesions, inverted tumours and substaging. The concept of neuroendocrine tumours will be explained precisely.
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- 2022
177. Access and quality of biomarker testing for precision oncology in Europe
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Nicola Normanno, Kathi Apostolidis, Audrey Wolf, Raed Al Dieri, Zandra Deans, Jenni Fairley, Jörg Maas, Antonio Martinez, Holger Moch, Søren Nielsen, Thomas Pilz, Etienne Rouleau, Simon Patton, Victoria Williams, University of Zurich, and Normanno, Nicola
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Cancer Research ,Genomic profiling ,610 Medicine & health ,Precision oncology ,Medical Oncology ,External quality assessment ,Europe ,Oncology ,10049 Institute of Pathology and Molecular Pathology ,Next generation sequencing ,Neoplasms ,Humans ,2730 Oncology ,1306 Cancer Research ,Precision Medicine ,Biomarkers - Abstract
BackgroundPredictive biomarkers are essential for selecting the best therapeutic strategy in patients with cancer. The International Quality Network for Pathology, the European Cancer Patient Coalition and the European Federation of Pharmaceuticals Industries and Associations evaluated the access to and quality of biomarker testing across Europe.MethodsData sources included surveys of 141 laboratory managers and 1.665 patients, and 58 in-depth interviews with laboratory managers, physicians and payers. Four access metrics (laboratory access, test availability, test reimbursement, test order rate) and three quality metrics (quality scheme participation, laboratory accreditation, test turnaround time) were applied to rank the results.ResultsThe access to precision medicines is higher in countries with public national reimbursement processes in place. Lack of diagnostic laboratory infrastructure, inefficient organization and/or insufficient public reimbursement narrow the access to single biomarker tests in many European countries. In countries with limited public reimbursement, pharma and patients’ out of pocket were the primary funding sources for testing. Uptake of multi-biomarker next generation sequencing (NGS) is highly varied, ranging from 0% to >50%. Financial constraints, a lack of NGS testing capabilities and the failure to include NGS testing in the guidelines represent the main barriers to NGS implementation. The quality of biomarker testing is highest in Western and Northern Europe, with more than 90% of laboratories participating in quality assurance schemes.ConclusionsOur data clearly indicate the need for a call to action to ensure the clinical implementation of precision medicine in Europe.
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- 2022
178. Histologische Subtypen des Nierenzellkarzinoms
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A. Hartmann, Holger Moch, I. Polifka, Abbas Agaimy, University of Zurich, and Hartmann, A
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0301 basic medicine ,Oncology ,medicine.medical_specialty ,business.industry ,610 Medicine & health ,urologic and male genital diseases ,medicine.disease ,female genital diseases and pregnancy complications ,Pathology and Forensic Medicine ,2734 Pathology and Forensic Medicine ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Immunophenotyping ,Renal cell carcinoma ,10049 Institute of Pathology and Molecular Pathology ,030220 oncology & carcinogenesis ,Internal medicine ,medicine ,Who classification ,business - Abstract
BACKGROUND The classification of renal cell carcinoma (RCC) has changed remarkably in recent years. OBJECTIVES This is a short overview of the classification of RCC, focusing on new developments. MATERIALS AND METHODS A literature search was performed resulting in an overview of the classification of RCC. Emerging entities were discussed in detail. RESULTS Apart from the RCC subtypes in the WHO classification of 2016, several emerging entities came up over the last few years that are characterized by typical morphology, immunophenotype, and especially specific genetic alterations. CONCLUSION Precise classification of RCC is the key to better prognostic assessment with potential tumor-specific therapy and plays an important role in the recognition of possible association with hereditary tumor syndromes.
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- 2021
179. Towards a new WHO classification of renal cell tumor: what the clinician needs to know—a narrative review
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Veronica Mollica, Marina Scarpelli, Alessia Cimadamore, Francesco Massari, Matteo Santoni, Antonio Lopez-Beltran, Rodolfo Montironi, Holger Moch, Liang Cheng, University of Zurich, Cimadamore, Alessia, Cimadamore A., Cheng L., Scarpelli M., Massari F., Mollica V., Santoni M., Lopez-Beltran A., Montironi R., and Moch H.
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2748 Urology ,0301 basic medicine ,Oncology ,medicine.medical_specialty ,Urology ,610 Medicine & health ,Anaplastic lymphoma kinase (ALK) ,Classification ,Clear cell RCC ,Emerging entities ,Fumarate hydratase (FH) ,Molecular pathology ,Non-clear cells RCC ,Renal cell carcinoma ,Succinate dehydrogenase (SDH) ,Von hippel-lindau gene (VHL) ,urologic and male genital diseases ,Renal neoplasm ,Renal medullary carcinoma ,03 medical and health sciences ,Collecting duct carcinoma ,0302 clinical medicine ,10049 Institute of Pathology and Molecular Pathology ,Internal medicine ,Medicine ,Pathological ,business.industry ,Emerging entitie ,Cancer ,2743 Reproductive Medicine ,medicine.disease ,female genital diseases and pregnancy complications ,030104 developmental biology ,Reproductive Medicine ,030220 oncology & carcinogenesis ,Review Article on Update on Molecular Classification and Individualized Treatments of Genitourinary Tumors ,business ,Who classification - Abstract
In 1952, renal cell carcinomas had been divided into 2 categories-clear cell or granular cell-depending upon their cytoplasmic staining characteristics. In the following years, the inventory of renal epithelial tumors has expanded by the addition of tumors named by their architectural pattern (i.e., papillary RCC, tubulocystic RCC), anatomic location (i.e., collecting duct carcinoma, renal medullary carcinoma), associated diseases (i.e., acquired cystic disease-associated RCCs). With the extensive application of molecular diagnostic techniques, it becomes possible to detect genetic distinctions between various types of renal neoplasm and discover new entities, otherwise misdiagnosed or diagnosed as unclassified RCC. Some tumors such as ALK rearrangement-associated RCC, MiT family translocation renal carcinomas, SDH-deficient renal cancer or FH-deficient RCC, are defined by their molecular characteristics. The most recent World Health Organization (WHO) classification of renal neoplasms account for more than 50 entities and provisional entities. New entities might be included in the upcoming WHO classification. The aim of this review is to summarise and discuss the newly acquired data and evidence on the clinical, pathological, molecular features and on the prognosis of new RCC entities, which will hopefully increase the awareness and the acceptance of these entities among clinicians and improve prognostication for individual patients.
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- 2021
180. The Role of Frozen Section Examination During Inguinal Exploration in Men with Inconclusive Testicular Tumors: A Systematic Review and Meta-analysis
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Holger Moch, Joerg Beyer, Daniel Eberli, Vijay A.C. Ramani, Benedikt Kranzbühler, Peter K. Bode, Christian D. Fankhauser, Pedro Oliveira, Thomas Hermanns, and Lisa Roth
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Male ,Frozen section procedure ,medicine.medical_specialty ,business.industry ,Urology ,030232 urology & nephrology ,Testicular Germ Cell Tumor ,03 medical and health sciences ,0302 clinical medicine ,Testicular Neoplasms ,Radical orchiectomy ,030220 oncology & carcinogenesis ,Meta-analysis ,Cohort ,Biomarkers, Tumor ,Frozen Sections ,Humans ,Medicine ,In patient ,Orchiectomy ,Radiology ,business ,Patient summary ,Retrospective Studies - Abstract
For inconclusive testicular tumors with negative tumor markers, frozen section examination (FSE) during inguinal exploration is recommended. However, FSE is time-consuming and therefore often not requested. Furthermore, the exact diagnostic benefit remains poorly defined. We performed a systematic review and meta-analysis summarizing 12 published studies and our own series of FSE in patients with inconclusive testicular tumors, resulting in a cohort of 1052 FSEs. FSE showed sensitivity of 99% and specificity of 96% with a positive predictive value of 98% and a negative predictive value of 97%. Most importantly, one-third of all testicular tumors investigated were correctly identified as being suitable for testis-sparing surgery and orchiectomy could be avoided. For patients with inconclusive testicular tumors, FSE is useful for deciding whether testis-sparing surgery is an option or whether radical orchiectomy should be performed. Thus, these patients should be optimally treated in institutions where FSE is available. PATIENT SUMMARY: We found that intraoperative examination of a frozen section is useful in deciding on whether the entire or only parts of the testicle can be removed. We conclude that frozen section examination should be offered to men with small testicular lesions and negative tumor markers.
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- 2021
181. CD39+PD-1+CD8+ T cells mediate metastatic dormancy in breast cancer
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Maries van den Broek, Paulino Tallón de Lara, Stefanie Hiltbrunner, Isabelle Glarner, Marijne Vermeer, Héctor Castañón, Virginia Cecconi, Hideo Yagita, Holger Moch, Nicolás Gonzalo Núñez, Joaquín Urdinez, Farkhondeh Movahedian Attar, Sonia Tugues, Bettina Sobottka, Burkhard Becher, Karina Silina, University of Zurich, and van den Broek, Maries
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0301 basic medicine ,Adoptive cell transfer ,medicine.medical_treatment ,Science ,Programmed Cell Death 1 Receptor ,General Physics and Astronomy ,Breast Neoplasms ,610 Medicine & health ,1600 General Chemistry ,CD8-Positive T-Lymphocytes ,Biology ,Article ,General Biochemistry, Genetics and Molecular Biology ,Metastasis ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,Antigens, CD ,Mice, Inbred NOD ,1300 General Biochemistry, Genetics and Molecular Biology ,Cell Line, Tumor ,10049 Institute of Pathology and Molecular Pathology ,medicine ,Animals ,Humans ,Cytotoxic T cell ,Neoplasm Metastasis ,Lung ,Mice, Knockout ,Mice, Inbred BALB C ,Multidisciplinary ,Apyrase ,Mammary Neoplasms, Experimental ,Cancer ,General Chemistry ,Immunotherapy ,medicine.disease ,3100 General Physics and Astronomy ,3. Good health ,030104 developmental biology ,030220 oncology & carcinogenesis ,Cancer cell ,Cancer research ,Tumour immunology ,CD8 - Abstract
Some breast tumors metastasize aggressively whereas others remain dormant for years. The mechanism governing metastatic dormancy remains largely unknown. Through high-parametric single-cell mapping in mice, we identify a discrete population of CD39+PD-1+CD8+ T cells in primary tumors and in dormant metastasis, which is hardly found in aggressively metastasizing tumors. Using blocking antibodies, we find that dormancy depends on TNFα and IFNγ. Immunotherapy reduces the number of dormant cancer cells in the lungs. Adoptive transfer of purified CD39+PD-1+CD8+ T cells prevents metastatic outgrowth. In human breast cancer, the frequency of CD39+PD-1+CD8+ but not total CD8+ T cells correlates with delayed metastatic relapse after resection (disease-free survival), thus underlining the biological relevance of CD39+PD-1+CD8+ T cells for controlling experimental and human breast cancer. Thus, we suggest that a primary breast tumor could prime a systemic, CD39+PD-1+CD8+ T cell response that favors metastatic dormancy in the lungs., Dormancy of disseminated cancer cells has been described in patients with breast cancer and associated with late metastatic relapses. Here the authors show that CD39+PD-1+CD8+ T cells correlate with increased disease free survival post-resection in breast cancer patients, and promote dormancy in a preclinical model.
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- 2021
182. Tracing Clonal Dynamics Reveals that Two- and Three-dimensional Patient-derived Cell Models Capture Tumor Heterogeneity of Clear Cell Renal Cell Carcinoma
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Jack Kuipers, Holger Moch, Peter K. Bode, Niko Beerenwinkel, Francesca Chiovaro, Markus Rechsteiner, Chantal Pauli, Abdullah Kahraman, Viktor H. Koelzer, Claudia Corrò, Nora C. Toussaint, Wolfgang Moritz, Peter Schraml, Adriana von Teichman, Hella A. Bolck, University of Zurich, and Schraml, Peter
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2748 Urology ,Tumor heterogeneity ,Urology ,Cell ,030232 urology & nephrology ,Renal cancer ,Patient-derived models ,Clonal dynamics ,Personalized medicine ,610 Medicine & health ,Computational biology ,Evolution, Molecular ,Genetic Heterogeneity ,03 medical and health sciences ,0302 clinical medicine ,10049 Institute of Pathology and Molecular Pathology ,Biomarkers, Tumor ,Humans ,Medicine ,Precision Medicine ,Carcinoma, Renal Cell ,business.industry ,Cancer ,Precision medicine ,medicine.disease ,Kidney Neoplasms ,Biomarker (cell) ,Clear cell renal cell carcinoma ,medicine.anatomical_structure ,Cell culture ,030220 oncology & carcinogenesis ,Cancer cell ,business - Abstract
Background Extensive DNA sequencing has led to an unprecedented view of the diversity of individual genomes and their evolution among patients with clear cell renal cell carcinoma (ccRCC). Objective To understand subclonal architecture and dynamics of patient-derived two-dimensional (2D) and three-dimensional (3D) ccRCC models in vitro, in order to determine whether they mirror ccRCC inter- and intratumor heterogeneity. Design, setting, and participants We have established a comprehensive platform of living renal cancer cell models from ccRCC surgical specimens. Outcome measurements and statistical analysis We confirmed the concordance of 2D and 3D patient-derived cell (PDC) models with the original tumor tissue in terms of histology, biomarker expression, cancer driver mutations, and copy number alterations. We addressed inter- and intrapatient heterogeneity by analyzing clonal dynamics during serial passaging. Results and limitations In-depth genetic characterization verified the presence of heterogeneous cell populations, and revealed a high degree of similarity between subclonal compositions of monolayer and organoid cell cultures and the corresponding parental ccRCCs. Clonal dynamics were evident during serial passaging of cells in vitro, suggesting that PDC cultures can offer insights into evolutionary potential and treatment susceptibility of ccRCC subclones in vivo. Proof-of-concept drug profiling using selected ccRCC-targeted therapy agents highlighted patient-specific vulnerabilities in PDC models that could not be anticipated by interrogating commercially available cell lines. Conclusions We demonstrate that PDC models mirror inter- and intratumor heterogeneity of ccRCC in vitro. Based on our findings, we envision that the use of these models will advance our understanding of the trajectories that cause genetic diversity and their consequences for treatment on an individual level. Patient summary In this study, we developed two- and three-dimensional patient-derived models from clear cell renal cell carcinoma (ccRCC) as “mini-tumors in a dish.” We show that these cell models retain important features of the human ccRCCs such as the profound tumor heterogeneity, thus highlighting their importance for cancer research and precision medicine., European Urology Focus, 7 (1), ISSN:2405-4569
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- 2021
183. Chromophobe renal cell carcinoma: current and controversial issues
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Holger Moch, Riuko Ohashi, University of Zurich, and Moch, Holger
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0301 basic medicine ,Angiomyolipoma ,Chromophobe Renal Cell Carcinoma ,610 Medicine & health ,Chromophobe cell ,urologic and male genital diseases ,Pathology and Forensic Medicine ,Metastasis ,Diagnosis, Differential ,03 medical and health sciences ,0302 clinical medicine ,Germline mutation ,Renal cell carcinoma ,10049 Institute of Pathology and Molecular Pathology ,Adenoma, Oxyphilic ,Humans ,Medicine ,Oncocytoma ,Carcinoma, Renal Cell ,business.industry ,Molecular pathology ,medicine.disease ,Kidney Neoplasms ,female genital diseases and pregnancy complications ,2734 Pathology and Forensic Medicine ,030104 developmental biology ,030220 oncology & carcinogenesis ,Cancer research ,business - Abstract
It has been 35 years since Professor Thoenes and his colleagues discovered chromophobe renal cell carcinoma (RCC). Since then, our knowledge about this tumour entity has changed and novel tumour entities have been discovered. The aim of this review is to discuss recent molecular findings and open questions in diagnosing chromophobe-like/oncocytic neoplasms. The broader differential diagnosis of chromophobe-like and oncocytoma-like neoplasms includes SDH-deficient renal cell carcinoma, fumarate hydratase (FH) deficient RCC, epitheloid angiomyolipoma ('oncocytoma like'), MiT family translocation RCC and the emerging entity of eosinophilic solid and cystic renal cell carcinoma. After separation of these tumours from chromophobe RCC, it becomes evident that chromophobe RCC are low malignant tumours with a 5-6% risk of metastasis. Recent next generation sequencing (NGS) and DNA methylation profiling studies have confirmed Thoenes' theory of a distal tubule derived origin of chromophobe RCC and renal oncocytomas. Comprehensive genomic analyses of chromophobe RCC have demonstrated a low somatic mutation rate and identified TP53 and PTEN as the most frequently mutated genes, whereas 'unclassified' RCC with oncocytic or chromophobe-like features can show somatic inactivating mutations of TSC2 or activating mutations of MTOR as the primary molecular alterations. For the future, it would be desirable to create a category of 'oncocytic/chromophobe RCC, NOS' with the potential of further molecular studies for identification of TSC1/2 mutations in these rare tumours.
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- 2021
184. Autopsie und Religion: Die Sektion aus medizinischer, ethischer und religiöser Sicht
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Marcel Geisser, Mahmoud El Guindi, Satish Joshi, Janina Thym, Alberto Bondolfi, Wilfried Härle, Marian Eleganti, Refoel Guggenheim, Marcel Yair Ebel, Thomas Heiniger, Holger Moch, Brigitte Tag
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- 2014
185. Comprehensive Genomic Profiling of Carcinoma of Unknown Primary Origin: Retrospective Molecular Classification Considering the CUPISCO Study Design
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Holger Moch, Marlene Thomas, Andreas Beringer, Ethan Sokol, Alwin Krämer, Jeffrey S. Ross, Ferran Losa, Giulia Baciarello, Julia A. Elvin, Dexter X. Jin, Linda Mileshkin, Nhu Ngo, and University of Zurich
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0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,Cancer Diagnostics and Molecular Pathology ,Lung Neoplasms ,medicine.medical_treatment ,610 Medicine & health ,Targeted therapy ,law.invention ,Loss of heterozygosity ,03 medical and health sciences ,0302 clinical medicine ,Randomized controlled trial ,law ,Internal medicine ,10049 Institute of Pathology and Molecular Pathology ,Proto-Oncogene Proteins ,ROS1 ,Carcinoma ,Biomarkers, Tumor ,Medicine ,Unknown primary tumors ,Genetic profiling ,Humans ,Molecular targeted therapy ,Retrospective Studies ,business.industry ,Gene Expression Profiling ,Microsatellite instability ,Genomics ,Protein-Tyrosine Kinases ,medicine.disease ,Clinical trial ,030104 developmental biology ,030220 oncology & carcinogenesis ,Mutation ,Adenocarcinoma ,Neoplasms, Unknown Primary ,business - Abstract
Background Carcinoma of unknown primary origin (CUP) accounts for 2%–5% of newly diagnosed advanced malignancies, with chemotherapy as the standard of care. CUPISCO (NCT03498521) is an ongoing randomized trial using comprehensive genomic profiling (CGP) to assign patients with CUP to targeted or immunotherapy treatment arms based on genomic profiling. We performed a retrospective analysis of CUP cases referred for CGP to determine how many were potentially eligible for enrollment into an experimental CUPISCO arm. Materials and Methods Centrally reviewed adenocarcinoma and undifferentiated CUP specimens in the FoundationCore database were analyzed using the hybrid capture‐based FoundationOne CDx assay (mean coverage, >600×). Presence of genomic alterations, microsatellite instability (MSI), tumor mutational burden (TMB), genomic loss of heterozygosity (gLOH), and programmed death‐ligand 1 (PD‐L1) positivity were determined. Results A total of 96 of 303 patients (31.7%) could be matched to an experimental CUPISCO arm. Key genomic alterations included ERBB2 (7.3%), PIK3CA (6.3%), NF1 (5.6%), NF2 (4.6%), BRAF (4.3%), IDH1 (3.3%), PTEN, FGFR2, EGFR (3.6% each), MET (4.3%), CDK6 (3.0%), FBXW7, CDK4 (2.3% each), IDH2, RET, ROS1, NTRK (1.0% each), and ALK (0.7%). Median TMB was 3.75 mutations per megabase of DNA; 34 patients (11.6%) had a TMB ≥16 mutations per megabase. Three patients (1%) had high MSI, and 42 (14%) displayed high PD‐L1 expression (tumor proportion score ≥50%). gLOH could be assessed in 199 of 303 specimens; 19.6% had a score of >16%. Conclusions Thirty‐two percent of patients would have been eligible for targeted therapy in CUPISCO. Future studies, including additional biomarkers such as PD‐L1 positivity and gLOH, may identify a greater proportion potentially benefiting from CGP‐informed treatment. Clinical trial identification number. NCT03498521 Implications for Practice The findings of this retrospective analysis of carcinoma of unknown primary origin (CUP) cases validate the experimental treatment arms being used in the CUPISCO study (NCT03498521), an ongoing randomized trial using comprehensive genomic profiling to assign patients with CUP to targeted or immunotherapy treatment arms based on the presence of pathogenic genomic alterations. The findings also suggest that future studies including additional biomarkers and treatment arms, such as programmed death‐ligand 1 positivity and genomic loss of heterozygosity, may identify a greater proportion of patients with CUP potentially benefiting from comprehensive genomic profiling‐informed treatment., This article focuses on the ability of comprehensive genomic profiling to identify potentially targetable genetic alterations in cancers of unknown primary, based on the inclusion criteria for the CUPISCO clinical trial and aiming for more effective therapeutic options for patients.
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- 2020
186. WHO Classification of Tumours fifth edition: evolving issues in the classification, diagnosis, and prognostication of prostate cancer
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James G Kench, Mahul B Amin, Daniel M Berney, Eva M Compérat, Ian A Cree, Anthony J Gill, Arndt Hartmann, Santosh Menon, Holger Moch, George J Netto, Maria R Raspollini, Mark A Rubin, Puay Hoon Tan, Toyonori Tsuzuki, Samra Turjalic, Theo H van der Kwast, Ming Zhou, and John R Srigley
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Carcinoma, Ductal ,Male ,Prostatic Intraepithelial Neoplasia ,Histology ,Humans ,Prostatic Neoplasms ,Androgen Antagonists ,General Medicine ,World Health Organization ,Pathology and Forensic Medicine - Abstract
The fifth edition of the WHO Classification of Tumours of the Urinary and Male Genital Systems encompasses several updates to the classification and diagnosis of prostatic carcinoma as well as incorporating advancements in the assessment of its prognosis, including recent grading modifications. Some of the salient aspects include: (1) recognition that prostatic intraepithelial neoplasia (PIN)-like carcinoma is not synonymous with a pattern of ductal carcinoma, but better classified as a subtype of acinar adenocarcinoma; (2) a specific section on treatment-related neuroendocrine prostatic carcinoma in view of the tight correlation between androgen deprivation therapy and the development of prostatic carcinoma with neuroendocrine morphology, and the emerging data on lineage plasticity; (3) a terminology change of basal cell carcinoma to "adenoid cystic (basal cell) cell carcinoma" given the presence of an underlying MYB::NFIB gene fusion in many cases; (4) discussion of the current issues in the grading of acinar adenocarcinoma and the prognostic significance of cribriform growth patterns; and (5) more detailed coverage of intraductal carcinoma of prostate (IDC-P) reflecting our increased knowledge of this entity, while recommending the descriptive term atypical intraductal proliferation (AIP) for lesions falling short of IDC-P but containing more atypia than typically seen in high-grade prostatic intraepithelial neoplasia (HGPIN). Lesions previously regarded as cribriform patterns of HGPIN are now included in the AIP category. This review discusses these developments, summarising the existing literature, as well as the emerging morphological and molecular data that underpins the classification and prognostication of prostatic carcinoma.
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- 2022
187. An introduction to the WHO 5th edition 2022 classification of testicular tumours
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Daniel M Berney, Ian Cree, Vishal Rao, Holger Moch, John R Srigley, Toyonori Tsuzuki, Mahul B Amin, Eva M Comperat, Arndt Hartmann, Santosh Menon, George J Netto, Mark A Rubin, Samra Turajlic, Maria R Raspollini, and Satish K Tickoo
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Male ,Histology ,Testicular Neoplasms ,Humans ,Sex Cord-Gonadal Stromal Tumors ,General Medicine ,Carcinoid Tumor ,Neoplasms, Germ Cell and Embryonal ,World Health Organization ,Pathology and Forensic Medicine ,Seminoma - Abstract
The 5th edition of the World Health Organisation Blue Book was published recently and includes a comprehensive update on testicular tumours. This builds upon the work of the 4th edition, retaining its structure and main nomenclature, including the use of the term 'germ cell neoplasia in situ' (GCNIS) for the pre-invasive lesion of most germ cell tumours and division from those not derived from GCNIS. While there have been important developments in understanding the molecular underpinnings of testicular cancer, this updated classification paradigm and approach remains rooted in morphology. Nomenclature changes include replacement of the term 'primitive neuroectodermal tumour' by 'embryonic neuroectodermal tumour' based on the non-specificity of the former term and to separate these tumours clearly from Ewing sarcoma. Seminoma is placed in a germinoma family of tumours emphasising relation to those tumours at other sites. Criteria for the diagnosis of 'teratoma with somatic transformation' have been modified to not include variable field size assessments. The word 'carcinoid' has been changed to 'neuroendocrine tumour', with most examples in the testis now classified as 'prepubertal type testicular neuroendocrine tumour'. For sex cord-stromal tumours, the use of mitotic counts per high-power field has been changed to per mm2 for malignancy assessments, and the new entities, 'signet ring stromal tumour' and 'myoid gonadal stromal tumour', are defined. Well-differentiated papillary mesothelial tumour has now been defined as tumour type with a favourable prognosis. Sertoliform cystadenoma has been removed as an entity from testicular adnexal tumours and placed with Sertoli cell tumours.
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- 2022
188. MALDI Mass Spectrometry Imaging—Prognostic Pathways and Metabolites for Renal Cell Carcinomas
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Franziska Erlmeier, Na Sun, Jian Shen, Annette Feuchtinger, Achim Buck, Verena M. Prade, Thomas Kunzke, Peter Schraml, Holger Moch, Michael Autenrieth, Wilko Weichert, Arndt Hartmann, and Axel Walch
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Cancer Research ,Oncology ,clear-cell renal cell carcinoma ,papillary renal cell carcinoma ,chromophobe renal cell carcinoma ,mass spectrometry imaging ,metabolomics ,Article ,Chromophobe Renal Cell Carcinoma ,Clear-cell Renal Cell Carcinoma ,Mass Spectrometry Imaging ,Metabolomics ,Papillary Renal Cell Carcinoma ,ddc:610 ,urologic and male genital diseases ,neoplasms ,female genital diseases and pregnancy complications ,ddc - Abstract
Simple Summary Renal cell carcinoma (RCC) is the seventh most common cancer type and accounts for more than 80% of all renal tumors. Nevertheless, prognostic biomarkers for RCC are still missing. Therefore, we analyzed a large, multicenter cohort including the three most common RCC subtypes (clear cell RCC (ccRCC), papillary RCC (pRCC) and chromophobe RCC (chRCC)) by high mass resolution matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) for prognostic biomarker detection. This is a suitable method for biomarker detection for several tumor entities. We detected several pathways and metabolites with prognostic power for RCC in general and also for different RCC subtypes. Abstract High mass resolution matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) is a suitable method for biomarker detection for several tumor entities. Renal cell carcinoma (RCC) is the seventh most common cancer type and accounts for more than 80% of all renal tumors. Prognostic biomarkers for RCC are still missing. Therefore, we analyzed a large, multicenter cohort including the three most common RCC subtypes (clear cell RCC (ccRCC), papillary RCC (pRCC) and chromophobe RCC (chRCC)) by MALDI for prognostic biomarker detection. MALDI-Fourier-transform ion cyclotron resonance (FT-ICR)-MSI analysis was performed for renal carcinoma tissue sections from 782 patients. SPACiAL pipeline was integrated for automated co-registration of histological and molecular features. Kaplan–Meier analyses with overall survival as endpoint were executed to determine the metabolic features associated with clinical outcome. We detected several pathways and metabolites with prognostic power for RCC in general and also for different RCC subtypes.
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- 2022
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189. Eosinophilic solid and cystic renal cell carcinoma and renal cell carcinomas with TFEB alterations: a comparative study
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João Lobo, Markus Rechsteiner, Birgit M Helmchen, Niels J Rupp, Achim Weber, and Holger Moch
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Histology ,MART-1 Antigen ,Basic Helix-Loop-Helix Leucine Zipper Transcription Factors ,Biomarkers, Tumor ,Humans ,General Medicine ,Carcinoma, Renal Cell ,Immunohistochemistry ,Kidney Neoplasms ,Pathology and Forensic Medicine - Abstract
Eosinophilic solid and cystic renal cell carcinoma (ESC RCC) is a recently described renal tumour entity with frequent cytokeratin (CK)20 positivity, commonly harbouring TSC mutations. In contrast, frequency of CK20 expression and presence of TSC mutations are unclear in TFEB-amplified RCC and TFEB-translocated RCC, which frequently express Melan A. Herein, we provide a comparative analysis of six ESC RCC with four TFEB-amplified/translocated RCC.We assessed the frequency of CK20 and Melan A expression by immunohistochemistry and of TSC mutations by next-generation sequencing. TFEB alterations were confirmed by fluorescence in-situ hybridisation (FISH). All tumours showed voluminous eosinophilic cells with granular cytoplasm, prominent nucleoli, and most showed admixture of solid and cystic areas. CK20 expression was found in all six ESC RCC and in all RCCs with TFEB alterations. Melan A positivity was identified in five of six ESC RCC and four of four RCC with TFEB alterations. We found TSC mutations in two ESC RCCs, including in one case also harbouring a CIC fusion, and identified a TSC mutation in one TFEB-amplified RCC.ESC RCC represents an emerging renal tumour entity with some histological, immunohistochemical and molecular overlap to TFEB-amplified/translocated RCC. FISH for TFEB aids in this differential diagnosis in challenging cases.
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- 2022
190. HNF1β is a sensitive and specific novel marker for yolk sac tumor: a tissue microarray analysis of 601 testicular germ cell tumors
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Alessandra Gallo, Holger Moch, Ailsa Christiansen, Jörg Beyer, Christian D. Fankhauser, Peter K. Bode, Thomas Hermanns, University of Zurich, and Bode, Peter Karl
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Adult ,Male ,0301 basic medicine ,Pathology ,medicine.medical_specialty ,610 Medicine & health ,Biology ,Sensitivity and Specificity ,Pathology and Forensic Medicine ,Diagnosis, Differential ,Embryonal carcinoma ,03 medical and health sciences ,0302 clinical medicine ,Testicular Neoplasms ,10049 Institute of Pathology and Molecular Pathology ,Carcinoma, Embryonal ,Testis ,Biomarkers, Tumor ,medicine ,Humans ,Choriocarcinoma ,Yolk sac ,Hepatocyte Nuclear Factor 1-beta ,Intratubular germ cell neoplasia ,Endodermal Sinus Tumor ,Teratoma ,Seminoma ,medicine.disease ,Immunohistochemistry ,2734 Pathology and Forensic Medicine ,10062 Urological Clinic ,030104 developmental biology ,medicine.anatomical_structure ,Tissue Array Analysis ,030220 oncology & carcinogenesis ,embryonic structures ,Germ cell tumors ,Ovarian cancer ,Germ cell - Abstract
Hepatocyte Nuclear Factor 1 beta (HNF1β) is a transcription factor which plays an important role during early organogenesis, especially of the pancreato-biliary and urogenital tract. Furthermore, HNF1β is an established marker in the differential diagnosis of ovarian cancer and shows a distinct nuclear expression in the clear cell carcinoma subtype. Recently, it has been described in yolk sac tumor, which represents a common component in many non-seminomatous germ cell tumors. Due to its broad histologic diversity, the diagnosis may be challenging and additional tools are very helpful in the workup of germ cell tumors. Immunohistochemistry was used to study HNF1β expression in a tissue microarray (TMA) of 601 testicular germ cell tumors including seminoma, embryonal carcinoma, yolk sac tumor, choriocarcinoma, teratoma, germ cell neoplasia in situ (GCNIS), and normal tissue. The expression pattern was compared to glypican 3 (GPC3) and α-fetoprotein (AFP), two markers currently in use for the detection of yolk sac tumor. HNF1β showed a distinct nuclear staining in comparison to the cytoplasmic pattern of GPC3 and AFP. The sensitivity and specificity of HNF1β were 85.4% and 96.5%, of GPC3 83.3% and 90.7%, of AFP 62.5% and 97.7%. We conclude that HNF1β allows a reliable distinction of yolk sac tumor from other germ cell tumor components. Therefore, we propose HNF1β as a novel and robust marker in the immunohistochemical workup of testicular germ cell tumors.
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- 2020
191. Two distinct immunopathological profiles in autopsy lungs of COVID-19
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Tobias Junt, Gieri Cathomas, Kirsten D. Mertz, Viktor H. Koelzer, Holger Moch, Francesca Demichelis, Thomas Hoyler, Alexandar Tzankov, Nathalie Schwab, Niels Willi, Maurice Henkel, Werner Kempf, Angela Frank, Ronny Nienhold, Thomas Menter, Markus Tolnay, Veronika Zsikla, Mattia Barbareschi, Jasmin D. Haslbauer, Yari Ciani, University of Zurich, and Mertz, Kirsten D
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Male ,0301 basic medicine ,Pathology ,General Physics and Astronomy ,Autopsy ,CD8-Positive T-Lymphocytes ,medicine.disease_cause ,Transcriptome ,0302 clinical medicine ,Interferon ,Sequencing ,lcsh:Science ,Lung ,Coronavirus ,Aged, 80 and over ,Multidisciplinary ,Respiratory disease ,virus diseases ,Middle Aged ,Viral Load ,respiratory system ,3100 General Physics and Astronomy ,Vaccination ,030220 oncology & carcinogenesis ,Cytokines ,Female ,Infection ,Coronavirus Infections ,Viral load ,medicine.drug ,medicine.medical_specialty ,Immunopathogenesis ,Coronavirus disease 2019 (COVID-19) ,Science ,Pneumonia, Viral ,610 Medicine & health ,1600 General Chemistry ,Biology ,Article ,General Biochemistry, Genetics and Molecular Biology ,Betacoronavirus ,03 medical and health sciences ,Immune system ,1300 General Biochemistry, Genetics and Molecular Biology ,10049 Institute of Pathology and Molecular Pathology ,medicine ,Humans ,Pandemics ,Gene ,Aged ,SARS-CoV-2 ,business.industry ,Gene Expression Profiling ,Macrophages ,COVID-19 ,General Chemistry ,medicine.disease ,respiratory tract diseases ,Pneumonia ,030104 developmental biology ,Viral infection ,Normal lung ,Immunology ,lcsh:Q ,Interferons ,business ,CD8 - Abstract
Coronavirus Disease 19 (COVID-19) is a respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has grown to a worldwide pandemic with substantial mortality. Immune mediated damage has been proposed as a pathogenic factor, but immune responses in lungs of COVID-19 patients remain poorly characterized. Here we show transcriptomic, histologic and cellular profiles of post mortem COVID-19 (n = 34 tissues from 16 patients) and normal lung tissues (n = 9 tissues from 6 patients). Two distinct immunopathological reaction patterns of lethal COVID-19 are identified. One pattern shows high local expression of interferon stimulated genes (ISGhigh) and cytokines, high viral loads and limited pulmonary damage, the other pattern shows severely damaged lungs, low ISGs (ISGlow), low viral loads and abundant infiltrating activated CD8+ T cells and macrophages. ISGhigh patients die significantly earlier after hospitalization than ISGlow patients. Our study may point to distinct stages of progression of COVID-19 lung disease and highlights the need for peripheral blood biomarkers that inform about patient lung status and guide treatment., The immunopathological features of SARS-CoV-2 infection in the lungs remain unclear. Here, the authors provide a comprehensive characterization of post mortem lung tissues of COVID-19 patients and find two distinct patterns characterized by differential expression of interferon stimulated genes (ISGs), which correlate to viral loads, cytokines, lung damage and time of hospitalization, suggesting ISG profiles to mark disease progression
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- 2020
192. Mass Spectrometry Imaging Differentiates Chromophobe Renal Cell Carcinoma and Renal Oncocytoma with High Accuracy
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Kerstin Junker, Mark Kriegsmann, Holger Moch, Matthias M. Gaida, Peter Schirmacher, Christine Stoehr, Nadine Maurer, Rita Casadonte, Wilko Weichert, Gunhild Mechtersheimer, Arndt Hartmann, Franziska Erlmeier, Sören-Oliver Deininger, Albrecht Stenzinger, Joerg Kriegsmann, Kristina Schwamborn, Katharina Kriegsmann, Christiane Zgorzelski, University of Zurich, Kriegsmann, Mark, and Kriegsmann, Katharina
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0301 basic medicine ,Chromophobe Renal Cell Carcinoma ,610 Medicine & health ,mass spectrometry imaging ,Biology ,Cross-validation ,Mass spectrometry imaging ,Oncocytic renal tumors ,03 medical and health sciences ,0302 clinical medicine ,proteomics ,10049 Institute of Pathology and Molecular Pathology ,medicine ,Renal oncocytoma ,chromophobe renal cell carcinoma ,business.industry ,medicine.disease ,Linear discriminant analysis ,Random forest ,Support vector machine ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,2730 Oncology ,Differential diagnosis ,Nuclear medicine ,business ,renal oncocytoma ,Research Paper - Abstract
Background: While subtyping of the majority of malignant chromophobe renal cell carcinoma (cRCC) and benign renal oncocytoma (rO) is possible on morphology alone, additional histochemical, immunohistochemical or molecular investigations are required in a subset of cases. As currently used histochemical and immunohistological stains as well as genetic aberrations show considerable overlap in both tumors, additional techniques are required for differential diagnostics. Mass spectrometry imaging (MSI) combining the detection of multiple peptides with information about their localization in tissue may be a suitable technology to overcome this diagnostic challenge. Patients and Methods: Formalin-fixed paraffin embedded (FFPE) tissue specimens from cRCC (n=71) and rO (n=64) were analyzed by MSI. Data were classified by linear discriminant analysis (LDA), classification and regression trees (CART), k-nearest neighbors (KNN), support vector machine (SVM), and random forest (RF) algorithm with internal cross validation and visualized by t-distributed stochastic neighbor embedding (t-SNE). Most important variables for classification were identified and the classification algorithm was optimized. Results: Applying different machine learning algorithms on all m/z peaks, classification accuracy between cRCC and rO was 85%, 82%, 84%, 77% and 64% for RF, SVM, KNN, CART and LDA. Under the assumption that a reduction of m/z peaks would lead to improved classification accuracy, m/z peaks were ranked based on their variable importance. Reduction to six most important m/z peaks resulted in improved accuracy of 89%, 85%, 85% and 85% for RF, SVM, KNN, and LDA and remained at the level of 77% for CART. t-SNE showed clear separation of cRCC and rO after algorithm improvement. Conclusion: In summary, we acquired MSI data on FFPE tissue specimens of cRCC and rO, performed classification and detected most relevant biomarkers for the differential diagnosis of both diseases. MSI data might be a useful adjunct method in the differential diagnosis of cRCC and rO.
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- 2020
193. Granular necrosis: a distinctive form of cell death in malignant tumours
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Andrew Evans, Murali Varma, Gladell P. Paner, Holger Moch, Bungo Furusato, Guido Martignoni, Liang Cheng, Sean R. Williamson, Thomas M. Wheeler, John Yaxley, Lars Egevad, Hemamali Samaratunga, Chin Chen Pan, Gregory T. MacLennan, Katia R. M. Leite, Michelle Thunders, Theodorus van der Kwast, Toyonori Tsuzuki, John R. Srigley, Jae Y. Ro, Daniel M. Berney, and Brett Delahunt
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0301 basic medicine ,Leiomyosarcoma ,Programmed cell death ,Pathology ,medicine.medical_specialty ,sarcoma ,Necrosis ,Carcinoma, granular necrosis, high grade, necrosis, pathogenesis, prognosis, sarcoma ,Necroptosis ,Biology ,necrosis ,Pathology and Forensic Medicine ,03 medical and health sciences ,0302 clinical medicine ,Renal cell carcinoma ,Neoplasms ,medicine ,Humans ,Fibrinoid necrosis ,high grade ,granular necrosis ,Cell Death ,pathogenesis ,Carcinoma ,Karyorrhexis ,medicine.disease ,030104 developmental biology ,Coagulative necrosis ,030220 oncology & carcinogenesis ,prognosis ,medicine.symptom - Abstract
Foci of necrosis are frequently seen in malignant tumours and may be due to a variety of causes. Different types of necrosis are given various names based upon their morphological features and presumed pathogenesis, such as coagulative, liquefactive and fibrinoid necrosis. Here, we propose the term 'granular necrosis' (GN) for a specific form of tumour necrosis characterised by the presence of well-defined necrotic foci being sharply demarcated from adjacent viable tumour. A constant feature is loss of architecture resulting in an amorphous necrotic mass containing granular nuclear and cytoplasmic debris, without an associated neutrophilic infiltrate. There is usually extensive karyorrhexis, which in larger tumours is more prominent at the periphery. These foci are often microscopic but may range up to several millimetres or larger in size. This distinctive form of necrosis has been erroneously given a variety of names in the literature including coagulative necrosis and microscopic necrosis, which on the basis of the aforementioned gross and microscopic findings is inappropriate. It is apparent that this is a specific form of necrosis, hence the descriptive term 'granular necrosis' that differentiates this form of necrosis from other types. The presence of GN is recognised as occurring in a variety of tumour types, being commonly seen in renal cell carcinoma, where it has been shown to have independent prognostic significance. In some epithelial and stromal tumours of the uterus, the presence of GN also has prognostic significance and is a defining feature for the differentiation of uterine leiomyoma and leiomyosarcoma. The pathogenesis of GN is unresolved. It does not show the features of apoptosis and in recent studies has been shown to have some of the molecular changes associated with necroptosis.
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- 2020
194. CME-Sonografie 89: Differenzialdiagnose von Nierenraumforderungen
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Holger Moch, Martin Baumgartner, Andreas L. Serra, Jan Tuma, University of Zurich, and Tuma, Jan
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medicine.medical_specialty ,Kidney ,business.industry ,Renal cortex ,Ultrasound ,610 Medicine & health ,2700 General Medicine ,General Medicine ,030204 cardiovascular system & hematology ,medicine.disease ,030218 nuclear medicine & medical imaging ,Muscle hypertrophy ,03 medical and health sciences ,0302 clinical medicine ,medicine.anatomical_structure ,10036 Medical Clinic ,Renal cell carcinoma ,10049 Institute of Pathology and Molecular Pathology ,Parenchyma ,medicine ,Radiology ,Differential diagnosis ,business ,Renal sinus - Abstract
Zusammenfassung. Zystische und solide Veränderungen der Nieren sind in der Ultraschalldiagnostik häufig. Der solide Pseudotumor der Niere, der sog. Nierenparenchymzapfen, wird in bis 50 % der Patienten gefunden. Pathologisch-anatomisch handelt es sich entweder um einer Hypertrophie der Columna Bertini oder um einen ganzen Renkulus, der in den Sinus renalis hineingeruscht ist. Nierenzysten wurden in einem Sektionsgut bei 50 % der über 50-Jährigen gefunden. Die zystischen Veränderungen werden mit der Bosniak-Klassifikation in fünf Kategorien unterteilt. Diese Klassifikation ist mit CECT, CEMR und CEUS möglich. Die soliden Veränderungen werden ebenso mit diesen Verfahren beurteilt, die Unterscheidung ist hier jedoch schwieriger. Mit Messung der Echodichte im Ultraschall gelingt die Differenzierung der echoreichen Angiomyolipome von übrigen soliden Tumoren und Pseudotumoren. In der farbkodierten Doppler-Sonografie (FKDS) wird oft das klarzellige Nierenzellkarzinom mit vielen Tumorgefässen dargestellt, die übrigen Tumoren mit wenigen oder nur einzelnen Gefässen. In CEUS und TIC wird das klarzellige Nierenzellkarzinom als sehr stark perfundiert dargestellt, die Anflutung in der TIC ist oft schneller und stärker als in der umliegenden gesunden Nierenrinde. Die übrigen Tumoren sind meist schwächer perfundiert, besonders die papillären Karzinome sind deutlich schwächer als die Nierenrinde.
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- 2020
195. The single-cell pathology landscape of breast cancer
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H. Raza Ali, Zsuzsanna Varga, Savas D. Soysal, Walter P. Weber, Simone Muenst, Bernd Bodenmiller, Robert Mechera, Jana R. Fischer, Vito R T Zanotelli, Hartland W. Jackson, and Holger Moch
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0301 basic medicine ,Tumor microenvironment ,Pathology ,medicine.medical_specialty ,Multidisciplinary ,Stromal cell ,Tumour heterogeneity ,Genetic heterogeneity ,Biology ,medicine.disease ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Breast cancer ,Single-cell analysis ,Stroma ,030220 oncology & carcinogenesis ,medicine ,Survival rate - Abstract
Single-cell analyses have revealed extensive heterogeneity between and within human tumours1–4, but complex single-cell phenotypes and their spatial context are not at present reflected in the histological stratification that is the foundation of many clinical decisions. Here we use imaging mass cytometry5 to simultaneously quantify 35 biomarkers, resulting in 720 high-dimensional pathology images of tumour tissue from 352 patients with breast cancer, with long-term survival data available for 281 patients. Spatially resolved, single-cell analysis identified the phenotypes of tumour and stromal single cells, their organization and their heterogeneity, and enabled the cellular architecture of breast cancer tissue to be characterized on the basis of cellular composition and tissue organization. Our analysis reveals multicellular features of the tumour microenvironment and novel subgroups of breast cancer that are associated with distinct clinical outcomes. Thus, spatially resolved, single-cell analysis can characterize intratumour phenotypic heterogeneity in a disease-relevant manner, with the potential to inform patient-specific diagnosis. A single-cell, spatially resolved analysis of breast cancer demonstrates the heterogeneity of tumour and stroma tissue and provides a more-detailed method of patient classification than the current histology-based system.
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- 2020
196. Machine learning with autophagy-related proteins for discriminating renal cell carcinoma subtypes
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He Liu, Holger Moch, Zhaoyue He, Hans-Uwe Simon, University of Zurich, and Simon, Hans-Uwe
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ATG5 ,Autophagy-Related Proteins ,Gene Expression ,lcsh:Medicine ,610 Medicine & health ,Chromophobe cell ,Biology ,Machine learning ,computer.software_genre ,urologic and male genital diseases ,Article ,Autophagy-Related Protein 5 ,Tumour biomarkers ,Machine Learning ,03 medical and health sciences ,Basal (phylogenetics) ,0302 clinical medicine ,10049 Institute of Pathology and Molecular Pathology ,Autophagy ,Autophagy-Related Protein-1 Homolog ,Humans ,RNA, Messenger ,lcsh:Science ,Carcinoma, Renal Cell ,ATG16L1 ,030304 developmental biology ,1000 Multidisciplinary ,0303 health sciences ,Kidney diseases ,Multidisciplinary ,Tissue microarray ,business.industry ,lcsh:R ,Intracellular Signaling Peptides and Proteins ,Kidney Neoplasms ,female genital diseases and pregnancy complications ,3. Good health ,030220 oncology & carcinogenesis ,Immunohistochemistry ,lcsh:Q ,Artificial intelligence ,business ,Microtubule-Associated Proteins ,computer ,Clear cell - Abstract
Machine learning techniques have been previously applied for classification of tumors based largely on morphological features of tumor cells recognized in H&E images. Here, we tested the possibility of using numeric data acquired from software-based quantification of certain marker proteins, i.e. key autophagy proteins (ATGs), obtained from immunohistochemical (IHC) images of renal cell carcinomas (RCC). Using IHC staining and automated image quantification with a tissue microarray (TMA) of RCC, we found ATG1, ATG5 and microtubule-associated proteins 1A/1B light chain 3B (LC3B) were significantly reduced, suggesting a reduction in the basal level of autophagy with RCC. Notably, the levels of the ATG proteins expressed did not correspond to the mRNA levels expressed in these tissues. Applying a supervised machine learning algorithm, the K-Nearest Neighbor (KNN), to our quantified numeric data revealed that LC3B provided a strong measure for discriminating clear cell RCC (ccRCC). ATG5 and sequestosome-1 (SQSTM1/p62) could be used for classification of chromophobe RCC (crRCC). The quantitation of particular combinations of ATG1, ATG16L1, ATG5, LC3B and p62, all of which measure the basal level of autophagy, were able to discriminate among normal tissue, crRCC and ccRCC, suggesting that the basal level of autophagy would be a potentially useful parameter for RCC discrimination. In addition to our observation that the basal level of autophagy is reduced in RCC, our workflow from quantitative IHC analysis to machine learning could be considered as a potential complementary tool for the classification of RCC subtypes and also for other types of tumors for which precision medicine requires a characterization.
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- 2020
197. Integrated Analysis Of Immunotherapy Treated Clear Cell Renal Cell Carcinomas: An Exploratory Study
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Angela Frank, Juergen Hench, Ronny Nienhold, Melanie Sachs, Kirsten D. Mertz, Bettina Sobottka, Holger Moch, Pirmin Haeuptle, Marta Nowak, Abdullah Kahraman, Viktor H. Koelzer, and University of Zurich
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renal cell carcinoma ,Cancer Research ,medicine.medical_treatment ,Immunology ,Cell ,Copy number analysis ,610 Medicine & health ,CD8-Positive T-Lymphocytes ,B7-H1 Antigen ,Lymphocytes, Tumor-Infiltrating ,Immune system ,10049 Institute of Pathology and Molecular Pathology ,Clinical Studies ,Tumor Microenvironment ,medicine ,Humans ,Immunology and Allergy ,Carcinoma, Renal Cell ,Pharmacology ,Tumor microenvironment ,business.industry ,personalized medicine ,Immunotherapy ,medicine.disease ,Primary tumor ,Kidney Neoplasms ,medicine.anatomical_structure ,ComputingMethodologies_DOCUMENTANDTEXTPROCESSING ,Cancer research ,immune phenotype ,next-generation sequencing ,digital pathology ,business ,Clear cell ,CD8 - Abstract
Supplemental Digital Content is available in the text., Molecular or immunological differences between responders and nonresponders to immune checkpoint inhibitors (ICIs) of clear cell renal cell carcinomas (ccRCCs) remain incompletely understood. To address this question, we performed next-generation sequencing, methylation analysis, genome wide copy number analysis, targeted RNA sequencing and T-cell receptor sequencing, and we studied frequencies of tumor-infiltrating CD8+ T cells, presence of tertiary lymphoid structures (TLS) and PD-L1 expression in 8 treatment-naive ccRCC patients subsequently treated with ICI (3 responders, 5 nonresponders). Unexpectedly, we identified decreased frequencies of CD8+ tumor-infiltrating T cells and TLS, and a decreased expression of PD-L1 in ICI responders when compared with nonresponders. However, neither tumor-specific genetic alterations nor gene expression profiles correlated with response to ICI or the observed immune features. Our results underline the challenge to stratify ccRCC patients for immunotherapy based on routinely available pathologic primary tumor material, even with advanced technologies. Our findings emphasize the analysis of pretreated metastatic tissue in line with recent observations describing treatment effects on the tumor microenvironment. In addition, our data call for further investigation of additional parameters in a larger ccRCC cohort to understand the mechanistic implications of the observed differences in tumor-infiltrating CD8+ T cells, TLS, and PD-L1 expression.
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- 2022
198. The 2022 World Health Organization Classification of Tumors of the Urinary System and Male Genital Organs-Part B: Prostate and Urinary Tract Tumors
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George J. Netto, Mahul B. Amin, Daniel M. Berney, Eva M. Compérat, Anthony J. Gill, Arndt Hartmann, Santosh Menon, Maria R. Raspollini, Mark A. Rubin, John R. Srigley, Puay Hoon Tan, Satish K. Tickoo, Toyonori Tsuzuki, Samra Turajlic, Ian Cree, and Holger Moch
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Male ,Urologic Neoplasms ,Urology ,Prostate ,Humans ,Prognosis ,Urinary Tract ,World Health Organization ,610 Medicine & health - Abstract
The 2022 World Health Organization (WHO) classification of the urinary and male genital tumors was recently published by the International Agency for Research on Cancer. This fifth edition of the WHO "Blue Book" offers a comprehensive update on the terminology, epidemiology, pathogenesis, histopathology, diagnostic molecular pathology, and prognostic and predictive progress in genitourinary tumors. In this review, the editors of the fifth series volume on urologic and male genital neoplasms present a summary of the salient changes introduced to the classification of tumors of the prostate and the urinary tract.
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- 2022
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199. Reply to Yongbao Wei, Haijian Huang, and Liefu Ye's Letter to the Editor re: George J. Netto, Mahul B. Amin, Daniel M. Berney, et al. The 2022 World Health Organization Classification of Tumors of the Urinary System and Male Genital Organs-Part B: Prostate and Urinary Tract Tumors. Eur Urol. In press. https://doi.org/10.1016/j.eururo.2022.07.002
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Mark A. Rubin, Mahul B. Amin, Eva Compérat, Anthony Gill, Arndt Hartman, Santosh Menon, Maria Raspollini, John Srigley, Puay Hoon Tan, Satish Ticktoo, Toyonori Tsuzuki, Samra Turajlic, Ian Cree, Daniel Berney, Holger Moch, George J. Netto, University of Zurich, and Netto, George J
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Male ,2748 Urology ,Urologic Neoplasms ,Urology ,10049 Institute of Pathology and Molecular Pathology ,Prostate ,Humans ,Prostatic Neoplasms ,610 Medicine & health ,Urinary Tract ,World Health Organization - Published
- 2022
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200. Validation of a Novel Three-Dimensional (3D Fusion) Gross Sampling Protocol for Clear Cell Renal Cell Carcinoma to Overcome Intratumoral Heterogeneity: The Meet-Uro 18 Study
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Matteo Brunelli, Guido Martignoni, Giorgio Malpeli, Alessandro Volpe, Luca Cima, Maria Rosaria Raspollini, Mattia Barbareschi, Alessandro Tafuri, Giulia Masi, Luisa Barzon, Serena Ammendola, Manuela Villanova, Maria Angela Cerruto, Michele Milella, Sebastiano Buti, Melissa Bersanelli, Giuseppe Fornarini, Sara Elena Rebuzzi, Valerio Gaetano Vellone, Gabriele Gaggero, Giuseppe Procopio, Elena Verzoni, Sergio Bracarda, Martina Fanelli, Roberto Sabbatini, Rodolfo Passalacqua, Bruno Perrucci, Maria Olga Giganti, Maddalena Donini, Stefano Panni, Marcello Tucci, Veronica Prati, Cinzia Ortega, Anna Caliò, Albino Eccher, Filippo Alongi, Giovanni Pappagallo, Roberto Iacovelli, Alessandra Mosca, Paolo Umari, Ilaria Montagnani, Stefano Gobbo, Francesco Atzori, Enrico Munari, Marco Maruzzo, Umberto Basso, Francesco Pierconti, Carlo Patriarca, Piergiuseppe Colombo, Alberto Lapini, Giario Conti, Roberto Salvioni, Enrico Bollito, Andrea Cossarizza, Francesco Massari, Mimma Rizzo, Renato Franco, Federica Zito-Marino, Yoseba Aberasturi Plata, Francesca Galuppini, Marta Sbaraglia, Matteo Fassan, Angelo Paolo Dei Tos, Maurizio Colecchia, Holger Moch, Maurizio Scaltriti, Camillo Porta, Brett Delahunt, Gianluca Giannarini, Roberto Bortolus, Pasquale Rescigno, Giuseppe Luigi Banna, Alessio Signori, Miguel Angel Llaja Obispo, Roberto Perris, Alessandro Antonelli, Brunelli, Matteo, Martignoni, Guido, Malpeli, Giorgio, Volpe, Alessandro, Cima, Luca, Raspollini, Maria Rosaria, Barbareschi, Mattia, Tafuri, Alessandro, Masi, Giulia, Barzon, Luisa, Ammendola, Serena, Villanova, Manuela, Cerruto, Maria Angela, Milella, Michele, Buti, Sebastiano, Bersanelli, Melissa, Fornarini, Giuseppe, Rebuzzi, Sara Elena, Vellone, Valerio Gaetano, Gaggero, Gabriele, Procopio, Giuseppe, Verzoni, Elena, Bracarda, Sergio, Fanelli, Martina, Sabbatini, Roberto, Passalacqua, Rodolfo, Perrucci, Bruno, Giganti, Maria Olga, Donini, Maddalena, Panni, Stefano, Tucci, Marcello, Prati, Veronica, Ortega, Cinzia, Caliò, Anna, Eccher, Albino, Alongi, Filippo, Pappagallo, Giovanni, Iacovelli, Roberto, Mosca, Alessandra, Umari, Paolo, Montagnani, Ilaria, Gobbo, Stefano, Atzori, Francesco, Munari, Enrico, Maruzzo, Marco, Basso, Umberto, Pierconti, Francesco, Patriarca, Carlo, Colombo, Piergiuseppe, Lapini, Alberto, Conti, Giario, Salvioni, Roberto, Bollito, Enrico, Cossarizza, Andrea, Massari, Francesco, Rizzo, Mimma, Franco, Renato, Zito-Marino, Federica, Aberasturi Plata, Yoseba, Galuppini, Francesca, Sbaraglia, Marta, Fassan, Matteo, Dei Tos, Angelo Paolo, Colecchia, Maurizio, Moch, Holger, Scaltriti, Maurizio, Porta, Camillo, Delahunt, Brett, Giannarini, Gianluca, Bortolus, Roberto, Rescigno, Pasquale, Banna, Giuseppe Luigi, Signori, Alessio, Obispo, Miguel Angel Llaja, Perris, Roberto, Antonelli, Alessandro, Brunelli M., Martignoni G., Malpeli G., Volpe A., Cima L., Raspollini M.R., Barbareschi M., Tafuri A., Masi G., Barzon L., Ammendola S., Villanova M., Cerruto M.A., Milella M., Buti S., Bersanelli M., Fornarini G., Rebuzzi S.E., Vellone V.G., Gaggero G., Procopio G., Verzoni E., Bracarda S., Fanelli M., Sabbatini R., Passalacqua R., Perrucci B., Giganti M.O., Donini M., Panni S., Tucci M., Prati V., Ortega C., Calio A., Eccher A., Alongi F., Pappagallo G., Iacovelli R., Mosca A., Umari P., Montagnani I., Gobbo S., Atzori F., Munari E., Maruzzo M., Basso U., Pierconti F., Patriarca C., Colombo P., Lapini A., Conti G., Salvioni R., Bollito E., Cossarizza A., Massari F., Rizzo M., Franco R., Zito-Marino F., Plata Y.A., Galuppini F., Sbaraglia M., Fassan M., Dei Tos A.P., Colecchia M., Moch H., Scaltriti M., Porta C., Delahunt B., Giannarini G., Bortolus R., Rescigno P., Banna G.L., Signori A., Obispo M.A.L., Perris R., and Antonelli A.
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angiogenesis ,clear cell renal cell carcinoma ,tumor sampling ,intratumoral heterogeneity ,immunity ,immunohistochemistry ,Medicine (miscellaneous) ,angiogenesi - Abstract
We aimed to overcome intratumoral heterogeneity in clear cell renal cell carcinoma (clearRCC). One hundred cases of clearRCC were sampled. First, usual standard sampling was applied (1 block/cm of tumor); second, the whole tumor was sampled, and 0.6 mm cores were taken from each block to construct a tissue microarray; third, the residual tissue, mapped by taking pieces 0.5 × 0.5 cm, reconstructed the entire tumor mass. Precisely, six randomly derived pieces of tissues were placed in each cassette, with the number of cassettes being based on the diameter of the tumor (called multisite 3D fusion). Angiogenic and immune markers were tested. Routine 5231 tissue blocks were obtained. Multisite 3D fusion sections showed pattern A, homogeneous high vascular density (10%), pattern B, homogeneous low vascular density (8%) and pattern C, heterogeneous angiogenic signatures (82%). PD-L1 expression was seen as diffuse (7%), low (33%) and absent (60%). Tumor-infiltrating CD8 scored high in 25% (pattern hot), low in 65% (pattern weak) and zero in 10% of cases (pattern desert). Grading was upgraded in 26% of cases (G3–G4), necrosis and sarcomatoid/rhabdoid characters were observed in, respectively, 11 and 7% of cases after 3D fusion (p = 0.03). CD8 and PD-L1 immune expressions were higher in the undifferentiated G4/rhabdoid/sarcomatoid clearRCC subtypes (p = 0.03). Again, 22% of cases were set to intermediate to high risk of clinical recurrence due to new morphological findings of all aggressive G4, sarcomatoid/rhabdoid features by using 3D fusion compared to standard methods (p = 0.04). In conclusion, we propose an easy-to-apply multisite 3D fusion sampling that negates bias due to tumor heterogeneity.
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- 2022
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