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Article ; Online: Künstliche Intelligenz in der Pathologie – wie, wo und warum?

Schüffler, Peter / Steiger, Katja / Mogler, Carolin

Pathologie (Heidelberg, Germany)

2024 Volume 45, Issue 3, Page(s) 198–202

Abstract: Artificial intelligence promises many innovations and simplifications in pathology, but also raises just as many questions and uncertainties. In this article, we provide a brief overview of the current status, the goals already achieved by existing ... ...

Title translation	Artificial intelligence for pathology-how, where, and why?
Abstract	Artificial intelligence promises many innovations and simplifications in pathology, but also raises just as many questions and uncertainties. In this article, we provide a brief overview of the current status, the goals already achieved by existing algorithms, and the remaining challenges.
MeSH term(s)	Artificial Intelligence ; Humans ; Pathology/methods ; Pathology/trends ; Algorithms
Language	German
Publishing date	2024-03-12
Publishing country	Germany
Document type	English Abstract ; Journal Article ; Review
ISSN	2731-7196
ISSN (online)	2731-7196
DOI	10.1007/s00292-024-01314-9
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Article ; Online: Vergleichende Pathologie in der onkologischen Forschung.

Groll, Tanja / Aupperle-Lellbach, Heike / Mogler, Carolin / Steiger, Katja

Pathologie (Heidelberg, Germany)

2024 Volume 45, Issue 3, Page(s) 190–197

Abstract: Comparative experimental pathology is a research field at the interface of human and veterinary medicine. It is focused on the comparative study of similarities and differences between spontaneous and experimentally induced diseases in animals (animal ... ...

Title translation	Comparative pathology in oncology-Best practice.
Abstract	Comparative experimental pathology is a research field at the interface of human and veterinary medicine. It is focused on the comparative study of similarities and differences between spontaneous and experimentally induced diseases in animals (animal models) compared to human diseases. The use of animal models for studying human diseases is an essential component of biomedical research. Interdisciplinary teams with species-specific expertise should collaborate wherever possible and maintain close communication. Mutual openness, cooperation, and willingness to learn form the basis for a fruitful collaboration. Research projects jointly led by or involving both animal and human pathologists make a significant contribution to high-quality biomedical research. Such approaches are promising not only in oncological research, as outlined in this article, but also in other research areas where animal models are regularly used, such as infectiology, neurology, and developmental biology.
MeSH term(s)	Animals ; Humans ; Neoplasms/pathology ; Disease Models, Animal ; Medical Oncology/methods ; Biomedical Research ; Pathology
Language	German
Publishing date	2024-04-11
Publishing country	Germany
Document type	English Abstract ; Journal Article ; Review
ISSN	2731-7196
ISSN (online)	2731-7196
DOI	10.1007/s00292-024-01327-4
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Article ; Online: How to use AI in pathology.

Schüffler, Peter / Steiger, Katja / Weichert, Wilko

Genes, chromosomes & cancer

2023 Volume 62, Issue 9, Page(s) 564–567

Abstract: AI plays an important role in pathology, both in clinical practice supporting pathologists in their daily work, and in research discovering novel biomarkers for improved patient care. Still, AI is in its starting phase, and many pathology labs still need ...

Abstract	AI plays an important role in pathology, both in clinical practice supporting pathologists in their daily work, and in research discovering novel biomarkers for improved patient care. Still, AI is in its starting phase, and many pathology labs still need to transition to a digital workflow to be able to enjoy the benefits of AI. In this perspective, we explain the major benefits of AI in pathology, highlight key requirements that need to be met and example how to use it in a typical workflow.
MeSH term(s)	Humans ; Workflow ; Artificial Intelligence ; Pathology/methods
Language	English
Publishing date	2023-05-31
Publishing country	United States
Document type	Journal Article
ZDB-ID	1018988-9
ISSN	1098-2264 ; 1045-2257
ISSN (online)	1098-2264
ISSN	1045-2257
DOI	10.1002/gcc.23178
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Zs.A 2966: Show issues

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Article ; Online: Sensitive Positron Emission Tomography Imaging of PD-L1 Expression in Human Breast and Lung Carcinoma Xenografts Using the Radiometalated Peptide Ga-68-TRAP-WL12.

Quigley, Neil Gerard / Steiger, Katja / Färber, Stefanie Felicitas / Richter, Frauke / Weichert, Wilko / Notni, Johannes

Molecular pharmaceutics

2024 Volume 21, Issue 4, Page(s) 1827–1837

Abstract: Noninvasive imaging of the immune checkpoint protein programmed death ligand 1 (PD-L1; synonyms: CD274, B7-H1) holds great promise to improve patient selection and, thus, response rates for immune checkpoint therapy (ICT) with monoclonal antibodies ... ...

Abstract	Noninvasive imaging of the immune checkpoint protein programmed death ligand 1 (PD-L1; synonyms: CD274, B7-H1) holds great promise to improve patient selection and, thus, response rates for immune checkpoint therapy (ICT) with monoclonal antibodies targeting the PD1/PD-L1 axis. The PD-L1 specific peptide WL12 (cyclo(AcY-(
MeSH term(s)	Humans ; Animals ; Mice ; Gallium Radioisotopes/chemistry ; B7-H1 Antigen/metabolism ; Heterografts ; Tissue Distribution ; Peptides/chemistry ; Lung Neoplasms/diagnostic imaging ; Cell Line, Tumor ; Adenocarcinoma of Lung ; Positron-Emission Tomography/methods ; Lung/metabolism
Chemical Substances	Gallium-68 (98B30EPP5S) ; Gallium Radioisotopes ; B7-H1 Antigen ; Peptides
Language	English
Publishing date	2024-01-31
Publishing country	United States
Document type	Journal Article
ZDB-ID	2138405-8
ISSN	1543-8392 ; 1543-8384
ISSN (online)	1543-8392
ISSN	1543-8384
DOI	10.1021/acs.molpharmaceut.3c01128
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Zs.A 6250: Show issues

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Article ; Online: Comparison of assessment of programmed death-ligand 1 (PD-L1) status in triple-negative breast cancer biopsies and surgical specimens.

Noske, Aurelia / Steiger, Katja / Ballke, Simone / Kiechle, Marion / Oettler, Dirk / Roth, Wilfried / Weichert, Wilko

Journal of clinical pathology

2024 Volume 77, Issue 4, Page(s) 239–245

Abstract: Aims: Programmed death-ligand 1 (PD-L1) status in triple-negative breast cancer (TNBC) is important for immune checkpoint inhibitor therapies but may vary between different immunohistochemical assays, scorings and the type of specimen used for analysis.! ...

Abstract	Aims: Programmed death-ligand 1 (PD-L1) status in triple-negative breast cancer (TNBC) is important for immune checkpoint inhibitor therapies but may vary between different immunohistochemical assays, scorings and the type of specimen used for analysis. Methods: We compared the analytical concordance of three clinically relevant PD-L1 assays (VENTANA SP142, VENTANA SP263 and DAKO 22C3 pharmDx) assessing immune cell score (IC), tumour proportion score and combined positive score (CPS) in preoperative biopsies and resection specimens of primary TNBC. PD-L1 expression was scored on virtual whole slide images and compared with expression data from corresponding surgical specimens. Results: The mean PD-L1 positivity in TNBC biopsies defined as IC ≥1% and CPS ≥1 ranged between 11% and 61% with the lowest positivity for SP142 and highest for SP263. The corresponding surgical specimens showed overall higher positivity rates (53%-75%). When comparing biopsies with surgical specimens, the agreement for PD-L1 positivity with SP263 and 22C3 at IC score ≥1% and CPS ≥1 was fair (kappa 0.47-0.52) and poor for SP142 (kappa 0.15-0.19). Using CPS ≥10 cut-off, the agreement for SP263 was excellent (kappa 0.751) but poor for 22C3 (kappa 0.261). Spearman correlation coefficients ranged between 0.489 and 0.75 indicating a generally moderate to strong correlation between biopsies and surgical specimens for all assays and scores. Conclusions: We demonstrate high accordance between biopsies and surgical specimens for SP263 and 22C3 scoring but less for SP142. Generally, biopsies are suitable for PD-L1 testing in TNBC but the appropriate assay, scoring and cut-off must be considered.
MeSH term(s)	Humans ; B7-H1 Antigen/analysis ; Biomarkers, Tumor/analysis ; Biopsy ; Immunohistochemistry ; Ligands ; Lung Neoplasms/pathology ; Triple Negative Breast Neoplasms/surgery
Chemical Substances	B7-H1 Antigen ; Biomarkers, Tumor ; Ligands
Language	English
Publishing date	2024-03-20
Publishing country	England
Document type	Comparative Study ; Journal Article
ZDB-ID	80261-x
ISSN	1472-4146 ; 0021-9746
ISSN (online)	1472-4146
ISSN	0021-9746
DOI	10.1136/jcp-2022-208637
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Article ; Online: A critical role for Akt1 signaling in acute pancreatitis progression

Sarker, Rim Sj / Steiger, Katja

The Journal of pathology

2020 Volume 251, Issue 1, Page(s) 1–3

Abstract: Acute pancreatitis (AP) is an inflammatory disease of the pancreas that causes significant morbidity and mortality worldwide. Unfortunately, there is no specific treatment available to date. Several studies have previously shown that inhibitors of the ... ...

Abstract	Acute pancreatitis (AP) is an inflammatory disease of the pancreas that causes significant morbidity and mortality worldwide. Unfortunately, there is no specific treatment available to date. Several studies have previously shown that inhibitors of the PI3K/Akt axis downregulate the degree of inflammation in animal models of AP. However, studies on in vivo side-effects of such inhibitors are still lacking. In a recent issue of The Journal of Pathology, Chen, Malagola et al investigated if inhibition of Akt signaling plays a negative role in the regenerative phase of AP. They showed that treating AP mice with an Akt inhibitor (MK2206) impaired acinar regeneration and increased the development of acinar-to-ductal metaplasia. This is the first study to highlight the negative impact of an Akt inhibitor on cellular regeneration while simultaneously inhibiting inflammation in AP. The authors also suggested combining Akt activators to recover pancreatic regeneration. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
MeSH term(s)	Acute Disease ; Animals ; Humans ; Pancreas/metabolism ; Pancreas/pathology ; Pancreatic Neoplasms/metabolism ; Pancreatic Neoplasms/pathology ; Pancreatitis/metabolism ; Pancreatitis/pathology ; Proto-Oncogene Proteins c-akt/metabolism ; Signal Transduction/physiology
Chemical Substances	Proto-Oncogene Proteins c-akt (EC 2.7.11.1)
Language	English
Publishing date	2020-02-25
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	3119-7
ISSN	1096-9896 ; 0022-3417
ISSN (online)	1096-9896
ISSN	0022-3417
DOI	10.1002/path.5391
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Article ; Online: Digitalisierung der histopathologischen Routinediagnostik : Dos and Don’ts!

Iwuajoku, Viola / Haas, Anette / Ekici, Kübra / Khan, Mohammad Zaid / Stögbauer, Fabian / Steiger, Katja / Mogler, Carolin / Schüffler, Peter J

Pathologie (Heidelberg, Germany)

2024 Volume 45, Issue 2, Page(s) 98–105

Abstract: The implementation of digital histopathology in the laboratory marks a crucial milestone in the overall digital transformation of pathology. This shift offers a range of new possibilities, including access to extensive datasets for AI-assisted analyses, ... ...

Title translation	Digital transformation of a routine histopathology lab : Dos and don'ts!
Abstract	The implementation of digital histopathology in the laboratory marks a crucial milestone in the overall digital transformation of pathology. This shift offers a range of new possibilities, including access to extensive datasets for AI-assisted analyses, the flexibility of remote work and home office arrangements for specialists, and the expedited and simplified sharing of images and data for research, conferences, and tumor boards. However, the transition to a fully digital workflow involves significant technological and personnel-related efforts. It necessitates careful and adaptable change management to minimize disruptions, particularly in the personnel domain, and to prevent the loss of valuable potential from employees who may be resistant to change. This article consolidates our institute's experiences, highlighting technical and personnel-related challenges encountered during the transition to digital pathology. It also presents a comprehensive overview of potential difficulties at various interfaces when converting routine operations to a digital workflow.
MeSH term(s)	Workflow ; Pathology/organization & administration ; Laboratories, Clinical/organization & administration
Language	German
Publishing date	2024-01-08
Publishing country	Germany
Document type	English Abstract ; Journal Article ; Review
ISSN	2731-7196
ISSN (online)	2731-7196
DOI	10.1007/s00292-023-01291-5
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Article ; Online: The fusion oncogene VAV1-MYO1F triggers aberrant T-cell receptor signaling in vivo and drives peripheral T-cell lymphoma in mice.

Morrish, Emma / Wartewig, Tim / Kratzert, Andreas / Rosenbaum, Marc / Steiger, Katja / Ruland, Jürgen

European journal of immunology

2023 Volume 53, Issue 3, Page(s) e2250147

Abstract: VAV1-MYO1F is a recently identified gain-of-function fusion protein of the proto-oncogene Vav guanine nucleotide exchange factor 1 (VAV1) that is recurrently detected in T-cell non-Hodgkin's lymphoma (T-NHL) patients. However, the pathophysiological ... ...

Abstract	VAV1-MYO1F is a recently identified gain-of-function fusion protein of the proto-oncogene Vav guanine nucleotide exchange factor 1 (VAV1) that is recurrently detected in T-cell non-Hodgkin's lymphoma (T-NHL) patients. However, the pathophysiological functions of VAV1-MYO1F in lymphomagenesis are insufficiently defined. Therefore, we generated transgenic mouse models to conditionally express VAV1-MYO1F in T-cells in vivo. We demonstrate that VAV1-MYO1F triggers cell autonomous activation of T-cell signaling with an activation of the ERK, JNK, and AKT pathways. VAV1-MYO1F expression induces a T-cell activation phenotype with high surface expression of CD25, ICOS, CD44, PD-1, and decreased CD62L as well as aberrant T-cell differentiation, proliferation, and neoplastic transformation. Consequently, the VAV1-MYO1F expressing T-cells induce a malignant T lymphoproliferative disease with 100% penetrance in vivo that mimics key aspects of human peripheral T-cell lymphoma. These results demonstrate that the human T-cell oncogene VAV1-MYO1F is sufficient to trigger oncogenic T-cell signaling and neoplastic transformation, and moreover, it provides a new clinically relevant mouse model to explore the pathogenesis of and treatment concepts for human T-cell lymphoma.
MeSH term(s)	Mice ; Humans ; Animals ; Proto-Oncogene Proteins c-vav/genetics ; Proto-Oncogene Proteins c-vav/metabolism ; Lymphoma, T-Cell, Peripheral/genetics ; Signal Transduction ; Receptors, Antigen, T-Cell/genetics ; Receptors, Antigen, T-Cell/metabolism ; Mice, Transgenic ; Oncogenes ; Myosin Type I/genetics ; Myosin Type I/metabolism
Chemical Substances	Proto-Oncogene Proteins c-vav ; Receptors, Antigen, T-Cell ; VAV1 protein, human ; MYO1F protein, human ; Myosin Type I (EC 3.6.1.-) ; Vav1 protein, mouse ; Myo1f protein, mouse
Language	English
Publishing date	2023-02-15
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	120108-6
ISSN	1521-4141 ; 0014-2980
ISSN (online)	1521-4141
ISSN	0014-2980
DOI	10.1002/eji.202250147
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Zs.A 489: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Quantitative bioimaging of copper in frozen liver specimens from cats using laser ablation-inductively coupled plasma-mass spectrometry

Yamkate, Punyamanee / Funke, Sabrina / Steiger, Katja / Gold, Randi M / Lidbury, Jonathan A / Karst, Uwe / Steiner, Joerg M

Journal of Feline Medicine and Surgery. 2023 July, v. 25, no. 7 p.1098612X231186919-

2023

Abstract: The aim of this study was to assess laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) as a tool for measuring concentrations and determining accumulation of copper in frozen liver specimens from cats. Six frozen liver specimens were ...

Abstract	The aim of this study was to assess laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) as a tool for measuring concentrations and determining accumulation of copper in frozen liver specimens from cats. Six frozen liver specimens were evaluated by qualitative copper staining and quantitative flame atomic absorption spectroscopy. Tissue specimens were cryo-sectioned and quantitative bioimaging of copper was performed using LA-ICP-MS. Results were compared with those obtained using conventional methods. Of the six specimens, only one showed positive staining for copper with rhodanine. Using flame atomic absorption spectroscopy (FAAS), one specimen showed a deficient copper level (<100 µg/g dry weight), two specimens had copper within the reference interval (RI; 150–180 µg/g) and three specimens had copper concentrations above the RI. Bioimaging from LA-ICP-MS showed inhomogeneous distribution of hepatic copper. The areas with dense copper accumulation were represented as hotspots in the liver specimens. Hepatic copper quantification by LA-ICP-MS correlated well with copper quantified by FAAS (r = 0.96, P = 0.002). Our findings suggest that quantitative bioimaging by LA-ICP-MS could be used to demonstrate the distribution and concentration of copper in frozen liver specimens from cats. The distribution of copper in these specimens was inhomogeneous with dense accumulation represented as hotspots on tissue sections. A positive correlation of hepatic copper concentrations determined by LA-ICP-MS and FAAS was found. Further studies to establish an RI for hepatic copper using this technique and to further determine its clinical utility are warranted.
Keywords	atomic absorption spectrometry ; bioimaging ; cats ; copper ; liver ; medicine ; surgery ; Hepatic copper ; heavy metal ; atomic absorption spectroscopy ; copper staining ; laser ablation-inductively coupled plasma-mass spectrometry ; LA-ICP-MS ; quantitative bioimaging
Language	English
Dates of publication	2023-07
Publishing place	SAGE Publications
Document type	Article ; Online
ZDB-ID	2049047-1
ISSN	1532-2750 ; 1098-612X
ISSN (online)	1532-2750
ISSN	1098-612X
DOI	10.1177/1098612X231186919
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Article ; Online: The limits of molecular signatures for pancreatic ductal adenocarcinoma subtyping.

Lautizi, Manuela / Baumbach, Jan / Weichert, Wilko / Steiger, Katja / List, Markus / Pfarr, Nicole / Kacprowski, Tim

NAR cancer

2022 Volume 4, Issue 4, Page(s) zcac030

Abstract: Molecular signatures have been suggested as biomarkers to classify pancreatic ductal adenocarcinoma (PDAC) into two, three, four or five subtypes. Since the robustness of existing signatures is controversial, we performed a systematic evaluation of four ... ...

Abstract	Molecular signatures have been suggested as biomarkers to classify pancreatic ductal adenocarcinoma (PDAC) into two, three, four or five subtypes. Since the robustness of existing signatures is controversial, we performed a systematic evaluation of four established signatures for PDAC stratification across nine publicly available datasets. Clustering revealed inconsistency of subtypes across independent datasets and in some cases a different number of PDAC subgroups than in the original study, casting doubt on the actual number of existing subtypes. Next, we built sixteen classification models to investigate the ability of the signatures for tumor subtype prediction. The overall classification performance ranged from ∼35% to ∼90% accuracy, suggesting instability of the signatures. Notably, permuted subtypes and random gene sets achieved very similar performance. Cellular decomposition and functional pathway enrichment analysis revealed strong tissue-specificity of the predicted classes. Our study highlights severe limitations and inconsistencies that can be attributed to technical biases in sample preparation and tumor purity, suggesting that PDAC molecular signatures do not generalize across datasets. How stromal heterogeneity and immune compartment interplay in the diverging development of PDAC is still unclear. Therefore, a more mechanistic or a cross-platform multi-omic approach seems necessary to extract more robust and clinically exploitable insights.
Language	English
Publishing date	2022-10-17
Publishing country	England
Document type	Journal Article
ISSN	2632-8674
ISSN (online)	2632-8674
DOI	10.1093/narcan/zcac030
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