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Article ; Online: Classification and Treatment of Diseases in the Age of Genome Medicine Based on Pathway Pathology

Iver Petersen

International Journal of Molecular Sciences, Vol 22, Iss 9418, p

2021 Volume 9418

Abstract: The focus of pathology as a biomedical discipline is the identification of the pathomechanisms of diseases and the integration of this knowledge into routine diagnosis and classification. Standard tools are macroscopic and microscopic analysis ... ...

Abstract	The focus of pathology as a biomedical discipline is the identification of the pathomechanisms of diseases and the integration of this knowledge into routine diagnosis and classification. Standard tools are macroscopic and microscopic analysis complemented by immunohistochemistry and molecular pathology. So far, classification has been based on the paradigm of cellular pathology established by Rudolf Virchow and others more than 150 years ago, stating that diseases originate from diseased cells. This dogma is meanwhile challenged by the fact that cells can be fully reprogrammed. Many diseases are nowadays considered to originate from undifferentiated stem cells, induced into a diseased state by genetic or epigenetic alterations. In addition, the completion of the Human Genome Project, with the identification of more than 20.000 genes and a much higher number of gene variants and mutations, led to the concept that diseases are dominated by genetics/epigenetics rather than cells of origin. The axiom of cellular pathology, however, still holds true, as cells are the smallest animate units from which diseases originate. Medical doctors and researchers nowadays have to deal with a tremendous amount of data. The International Classification of Diseases will expand from 14.400 entities/codes in ICD-10 to more than 55.000 in ICD-11. In addition, large datasets generated by “genomics“, e.g., whole-genome sequencing, expression profiling or methylome analysis, are meanwhile not only applied in research but also introduced into clinical settings. It constitutes a major task to incorporate all the data into routine medical work. Pathway pathology may help solve this problem. It is based on the realization that diseases are characterized by three essential components: (i) cells of origin/cellular context and (ii) the alteration of cellular as well as (iii) molecular/signal transduction pathways. The concept is illustrated by elaborating on two key cellular pathways, i.e., the cellular senescence of normal cells and the ...
Keywords	Leonard Hayflick ; Rudolf Virchow ; Manfred Dietel ; cellular pathology ; predictive pathology ; genome medicine ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	610
Language	English
Publishing date	2021-08-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Classification and Treatment of Diseases in the Age of Genome Medicine Based on Pathway Pathology.

Petersen, Iver

International journal of molecular sciences

2021 Volume 22, Issue 17

Abstract	The focus of pathology as a biomedical discipline is the identification of the pathomechanisms of diseases and the integration of this knowledge into routine diagnosis and classification. Standard tools are macroscopic and microscopic analysis complemented by immunohistochemistry and molecular pathology. So far, classification has been based on the paradigm of cellular pathology established by Rudolf Virchow and others more than 150 years ago, stating that diseases originate from diseased cells. This dogma is meanwhile challenged by the fact that cells can be fully reprogrammed. Many diseases are nowadays considered to originate from undifferentiated stem cells, induced into a diseased state by genetic or epigenetic alterations. In addition, the completion of the Human Genome Project, with the identification of more than 20.000 genes and a much higher number of gene variants and mutations, led to the concept that diseases are dominated by genetics/epigenetics rather than cells of origin. The axiom of cellular pathology, however, still holds true, as cells are the smallest animate units from which diseases originate. Medical doctors and researchers nowadays have to deal with a tremendous amount of data. The International Classification of Diseases will expand from 14.400 entities/codes in ICD-10 to more than 55.000 in ICD-11. In addition, large datasets generated by "genomics", e.g., whole-genome sequencing, expression profiling or methylome analysis, are meanwhile not only applied in research but also introduced into clinical settings. It constitutes a major task to incorporate all the data into routine medical work. Pathway pathology may help solve this problem. It is based on the realization that diseases are characterized by three essential components: (i) cells of origin/cellular context and (ii) the alteration of cellular as well as (iii) molecular/signal transduction pathways. The concept is illustrated by elaborating on two key cellular pathways, i.e., the cellular senescence of normal cells and the immortality of cancer cells, and by contrasting single cell/single pathway diseases, such as mycoplasma and coughing pneumonia, with complex diseases such as cancer, with multiple cell types as well as multiple affected cellular and signaling pathways. Importantly, the concept of pathway pathology is not just intended to classify disease, but also to conceive new treatment modalities. This article is dedicated to Dr. Leonard Hayflick, who made basic discoveries in pathway pathology not only by identifying cells causing disease (Mycoplasma pneumoniae) and establishing cell strains for treating disease (WI-38 for viral vaccines), but also by first describing cellular senescence and immortality.
MeSH term(s)	Disease/genetics ; Genome, Human ; Humans ; Molecular Targeted Therapy ; Precision Medicine ; Signal Transduction
Language	English
Publishing date	2021-08-30
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms22179418
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Article ; Online: Predictive pathology of lung cancer immunotherapy response.

Petersen, Iver

The Lancet. Respiratory medicine

2018 Volume 6, Issue 10, Page(s) 731–733

MeSH term(s)	Carcinoma, Non-Small-Cell Lung ; Humans ; Immunotherapy ; Lung Neoplasms ; Programmed Cell Death 1 Receptor ; Retrospective Studies
Chemical Substances	Programmed Cell Death 1 Receptor
Language	English
Publishing date	2018-09-26
Publishing country	England
Document type	Journal Article ; Comment
ZDB-ID	2686754-0
ISSN	2213-2619 ; 2213-2600
ISSN (online)	2213-2619
ISSN	2213-2600
DOI	10.1016/S2213-2600(18)30333-3
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Article ; Online: Update Thoraxpathologie 2020 : Bericht der Arbeitsgemeinschaft.

Petersen, Iver / Berezowska, Sabina

Der Pathologe

2020 Volume 41, Issue Suppl 2, Page(s) 184–186

Title translation	Update Thoracic Pathology 2020 : Report of the working group on thoracic pathology of the german society of pathology 2020.
MeSH term(s)	Germany ; Pathology ; Societies, Medical
Keywords	covid19
Language	German
Publishing date	2020-11-16
Publishing country	Germany
Document type	Journal Article
ZDB-ID	135954-x
ISSN	1432-1963 ; 0172-8113
ISSN (online)	1432-1963
ISSN	0172-8113
DOI	10.1007/s00292-020-00851-3
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Book ; Thesis: Ausschluß von ras-Mutationen bei der Entstehung Phenazetin-induzierter Urothelkarzinome

Petersen, Iver

1991

Author's details	vorgelegt von Iver Petersen
Size	39 Bl. : Ill.
Publishing country	Switzerland
Document type	Book ; Thesis
Thesis / German Habilitation thesis	Zürich, Univ., Diss., 1991
HBZ-ID	HT003951642
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Article ; Online: Adenoma detection rate using narrow-band imaging is inferior to high-definition white light colonoscopy in screening and surveillance colonoscopies in daily clinical care: A randomized controlled trial.

Bürger, Martin / Weber, Marko / Petersen, Iver / Stallmach, Andreas / Schmidt, Carsten

Medicine

2022 Volume 101, Issue 32, Page(s) e29858

Abstract: Background: Despite recent advances in endoscopic technology adenoma miss rate still is up to 20% contributing to interval cancers. Improved imaging modalities have been introduced to increase adenoma detection rate (ADR). Recently, narrow-band imaging ( ...

Abstract	Background: Despite recent advances in endoscopic technology adenoma miss rate still is up to 20% contributing to interval cancers. Improved imaging modalities have been introduced to increase adenoma detection rate (ADR). Recently, narrow-band imaging (NBI) (Exera II series, Olympus Corporation) was not significantly better than high-definition white light colonoscopy (HD-WLC). An improved second generation of NBI (190-NBI) is characterized by better illumination of the bowel lumen and may be associated with a higher ADR. Methods: We performed a prospective randomized study on patients referred to the Jena University Hospital for screening or surveillance colonoscopy between January 2015 and April 2017. Participating endoscopists were divided into 2 subgroups depending on their individual experience. Colonoscopy was performed by use of HD-WLC or 190-NBI upon withdrawal. Results: Five hundred fifty-three patients participated in the study. Eighty patients were excluded (insufficient bowel cleansing [n = 34], anticoagulation precluding polypectomy [n=15], partial colonic resection [n=9], other reasons [n = 22]). Mean age was 66.9 years (standard deviation 10.3 years), and 253 patients were male (53.5%). Bowel preparation and withdrawal time were not different. ADR among all subgroups was 39.4% using HD-WLC, but only 29.1% were using 190-NBI (P = .02). Number of polyps per patient was lower using 190-NBI than with HD-WLC (0.58 vs 0.86; P = .02). Subgroup analysis revealed that 190-NBI was inferior to HD-WLC only in unexperienced endoscopists. Conclusion: In our stud,y ADR was lower by use of 190-NBI. These differences persisted only in unexperienced investigators. 190-NBI seems to be more challenging regarding ADR, requiring more intensive training prior to implementing this technology in daily clinical care. Registration: ClinicalTrials.gov (identifier: NCT03081975).
MeSH term(s)	Adenoma/diagnostic imaging ; Aged ; Colonic Polyps/diagnostic imaging ; Colonoscopy/methods ; Female ; Humans ; Light ; Male ; Narrow Band Imaging/methods ; Prospective Studies
Language	English
Publishing date	2022-08-12
Publishing country	United States
Document type	Journal Article ; Randomized Controlled Trial
ZDB-ID	80184-7
ISSN	1536-5964 ; 0025-7974
ISSN (online)	1536-5964
ISSN	0025-7974
DOI	10.1097/MD.0000000000029858
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Article ; Online: Increased accuracy of FNA-based cytological diagnosis of pancreatic lesions by use of an ethanol-based fixative system: A STROBE compliant study.

Bürger, Martin / Heidrich, Antje / Petersen, Iver / Stallmach, Andreas / Schmidt, Carsten

Medicine

2022 Volume 101, Issue 36, Page(s) e30449

Abstract: EUS-guided fine needle aspiration cytology (FNA) is the gold standard of evaluation of solid pancreatic lesions. However, accuracy is generally low. The aim of this study was to compare the diagnostic yield of conventional cytology (CC) with liquid-based ...

Abstract	EUS-guided fine needle aspiration cytology (FNA) is the gold standard of evaluation of solid pancreatic lesions. However, accuracy is generally low. The aim of this study was to compare the diagnostic yield of conventional cytology (CC) with liquid-based cytological analysis using an ethanol based fixative system (LBC) without onsite cytopathological assessment. We performed a retrospective evaluation in patients referred to the Department of Interdisciplinary Endoscopy at Jena University Hospital for FNA of pancreatic masses between 2008 and 2015. LBC preservation of specimen was introduced in April 2011. Gold standard was defined as a surgically obtained histology or a patient follow-up of at least 1 year for diagnosis or exclusion of malignancy. 172 patients were included into the final analysis. Mean age was 64.8 years (SD 12.4 years), 105 patients were male. 107 lesions were malignant, while 65 lesions were benign. 89 specimens were evaluated by CC, whereas 83 specimens were processed by LBC. Liquid-based cytology performed significantly better than conventional cytology in terms of sensitivity (87.8% vs 67.2% (P = .021)), specificity (100% vs 87.1% (P = .047)) negative predictive value (NPV) (85% vs 58.7% (P = .009)) and accuracy (92.8% vs 74.2% (P = .001)). We observed no learning curve after implementation of LBC Liquid based cytology is a simple and inexpensive technique that helps improving sensitivity, specificity, NPV and accuracy over conventional cytology in fine needle aspirates from patients with pancreatic lesions. Therefore, this real-world evidence shows, that EUS-FNA specimen processing should be performed using LBC to achieve best possible results.
MeSH term(s)	Endoscopic Ultrasound-Guided Fine Needle Aspiration/methods ; Ethanol ; Female ; Fixatives ; Humans ; Male ; Middle Aged ; Pancreatic Neoplasms/diagnosis ; Pancreatic Neoplasms/pathology ; Retrospective Studies
Chemical Substances	Fixatives ; Ethanol (3K9958V90M)
Language	English
Publishing date	2022-08-17
Publishing country	United States
Document type	Journal Article
ZDB-ID	80184-7
ISSN	1536-5964 ; 0025-7974
ISSN (online)	1536-5964
ISSN	0025-7974
DOI	10.1097/MD.0000000000030449
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Book: Verbundprojekt: KMU-innovativ-3: Doppel-CISH- und LCD-Array-Analysen zum Nachweis von Translokationen (und z. T. auch Amplifikationen) in Sarkomen

Petersen, Iver

(Teilprojekt Universitätsklinikum Jena) ; Veröffentlichung der Ergebnisse von Forschungsvorhaben im BMBF-Programm ; Laufzeit: 01.05.2009 bis 30.06.2013

2014

Author's details	[Autor]/Projektleitung: Iver Petersen
Language	German
Size	9 Bl.
Publisher	Univ
Publishing place	Jena
Document type	Book
Note	Förderkennzeichen BMBF 0315509C. - Verbund-Nr. 01072677
Database	Library catalogue of the German National Library of Science and Technology (TIB), Hannover

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Book ; Online: Verbundprojekt: KMU-innovativ-3: Doppel-CISH- und LCD-Array-Analysen zum Nachweis von Translokationen (und z.T. auch Amplifikationen) in Sarkomen (Teilprojekt Universitätsklinikum Jena)

Petersen, Iver

Veröffentlichung der Ergebnisse von Forschungsvorhaben im BMBF-Programm ; Laufzeit: 01.05.2009 bis 30.06.2013

2014

Title variant	KMU-innovativ-3: Doppel-CISH- und LCD-Array-Analysen zum Nachweis von Translokationen (und z.T. auch Amplifikationen) in Sarkomen
Author's details	Autor/Projektleitung: Iver Petersen
Language	German
Size	Online-Ressource (10 S., 114 KB)
Publisher	Technische Informationsbibliothek u. Universitätsbibliothek ; Univ.-klinikum, Inst. für Pathologie
Publishing place	Hannover ; Jena
Document type	Book ; Online
Note	Förderkennzeichen BMBF 0315509C. - Verbund-Nr. 01072677 ; Unterschiede zwischen dem gedruckten Dokument und der elektronischen Ressource können nicht ausgeschlossen werden
Database	Library catalogue of the German National Library of Science and Technology (TIB), Hannover

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Article ; Online: Stem cell transcription factor SOX2 in synovial sarcoma and other soft tissue tumors.

Zayed, Heba / Petersen, Iver

Pathology, research and practice

2018 Volume 214, Issue 7, Page(s) 1000–1007

Abstract: Background: SOX2 has gained considerable interest as a pluripotency inducing gene. Co-transfection of SOX2 together with NANOG, KLF4 and c-MYC into adult fibroblasts was able to generate pluripotent stem cells. SOX2 has been reported to be expressed in ... ...

Abstract	Background: SOX2 has gained considerable interest as a pluripotency inducing gene. Co-transfection of SOX2 together with NANOG, KLF4 and c-MYC into adult fibroblasts was able to generate pluripotent stem cells. SOX2 has been reported to be expressed in synovial sarcoma, a tumor being characterized by the SS18-SSX gene fusion forming part of the SWI/SNF chromatin remodeling complex that affects histone methylation. The role of SOX2 in this tumor type as well as other soft tissue tumor entities however is still poorly characterized. We analyzed SOX2 protein expression in soft tissue tumors. Alongside we tested Histone H3 expression (H3K27me3) in SOX2 positive cases to investigate this epigenetic mark and its correlation with the SOX2 status and clinicopathological parameters. Methodology: In total, 60 samples of synovial sarcomas from the reference center for soft tissue tumors at the institute of pathology of the Jena University hospital were included into the study along with 343 other tissue tumors. Protein analysis was done by immunohistochemistry of tissue microarrays. All synovial sarcoma cases were confirmed by molecular testing using SS18 FISH break apart probes. Results: SOX2 reactivity was detectable in 35 synovial sarcoma cases (58.3%) while 25 (41.7%) were negative. Only 13 cases of the other 343 soft tissue tumors, varying from nodular fasciitis to undifferentiated pleomorphic sarcoma, revealed a SOX2 expression, 12 out of these were undifferentiated high grade sarcoma. There was no obvious correlation with the clinicopathological data. H3K27me3 immunohistochemistry of the synovial sarcoma cases revealed a high statistically significant correlation between SOX2 and H3K27me3 expression (p < 0,0005, Chi square test). Similar to SOX2, there was no correlation between H3K27me3 expression and tumor grade. Six SOX2 positive synovial sarcoma cases were analyzed by FISH using a SOX2/CEN3 dual color FISH probe. None of these cases revealed an amplification of the SOX2 gene. Conclusion: The data confirms previous studies reporting SOX2 and H3K27me3 expression in synovial sarcoma and reveals that both biomarkers are related to each other. It strengthens the notion that the tumor type is driven by epigenetic processes similar to those that are operating in pluripotent stem cells. The relevance of these parameters in the pathway pathology of synovial sarcoma, i.e. the timing and dosing of SOX2 and H3K27me3 expression initiated by the SS18-SSX driver mutation together with the interplay of these events with other signaling pathways, cellular mechanisms and additional mutations in tumor progression, will require further studies.
MeSH term(s)	Adult ; Aged ; Biomarkers, Tumor/metabolism ; Female ; Humans ; Male ; Middle Aged ; Oncogene Proteins, Fusion/genetics ; SOXB1 Transcription Factors/genetics ; SOXB1 Transcription Factors/metabolism ; Sarcoma, Synovial/genetics ; Sarcoma, Synovial/metabolism ; Soft Tissue Neoplasms/metabolism ; Soft Tissue Neoplasms/pathology ; Stem Cells/metabolism
Chemical Substances	Biomarkers, Tumor ; Oncogene Proteins, Fusion ; SOX2 protein, human ; SOXB1 Transcription Factors
Language	English
Publishing date	2018-05-04
Publishing country	Germany
Document type	Journal Article
ZDB-ID	391889-0
ISSN	1618-0631 ; 0344-0338
ISSN (online)	1618-0631
ISSN	0344-0338
DOI	10.1016/j.prp.2018.05.004
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