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A systematic analysis of commonly used antibodies in cancer diagnostics
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
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2014 (English)In: Histopathology, ISSN 0309-0167, E-ISSN 1365-2559, Vol. 64, no 2, 293-305 p.Article in journal (Refereed) Published
Abstract [en]

AimsImmunohistochemistry plays a pivotal role in cancer differential diagnostics. To identify the primary tumour from a metastasis specimen remains a significant challenge, despite the availability of an increasing number of antibodies. The aim of the present study was to provide evidence-based data on the diagnostic power of antibodies used frequently for clinical differential diagnostics. Methods and resultsA tissue microarray cohort comprising 940 tumour samples, of which 502 were metastatic lesions, representing tumours from 18 different organs and four non-localized cancer types, was analysed using immunohistochemistry with 27 well-established antibodies used in clinical differential diagnostics. Few antibodies, e.g. prostate-specific antigen and thyroglobulin, showed a cancer type-related sensitivity and specificity of more than 95%. A majority of the antibodies showed a low degree of sensitivity and specificity for defined cancer types. Combinations of antibodies provided limited added value for differential diagnostics of cancer types. ConclusionsThe results from analysing 27 diagnostic antibodies on consecutive sections of 940 defined tumours provide a unique repository of data that can empower a more optimal use of clinical immunohistochemistry. Our results highlight the benefit of immunohistochemistry and the unmet need for novel markers to improve differential diagnostics of cancer.

Place, publisher, year, edition, pages
2014. Vol. 64, no 2, 293-305 p.
Keyword [en]
biological tumour markers, differential diagnosis, immunohistochemistry, surgical pathology, tissue microarray analysis
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-216054DOI: 10.1111/his.12255ISI: 000328347800012OAI: oai:DiVA.org:uu-216054DiVA: diva2:689200
Note

De två (2) första författarna delar förstaförfattarskapet.

Available from: 2014-01-20 Created: 2014-01-17 Last updated: 2017-12-06Bibliographically approved
In thesis
1. Aspects of Gene Expression Profiling in Disease and Health
Open this publication in new window or tab >>Aspects of Gene Expression Profiling in Disease and Health
2017 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The aim of this thesis is to in various ways explore protein expression in human normal tissue and in cancer and to apply that knowledge in biomarker discovery.

In Paper I the prognostic significance of RNA-binding motif protein 3 (RBM3) is explored in malignant melanoma. To further evaluate the prognostic significance of RBM3 expression was assessed in 226 incident cases of malignant melanoma from the prospective populationbased cohort study Malmö Diet and Cancer Study using tissue microarray technique (TMA). RBM3 was shown to be down regulated in metastatic melanoma and high nuclear expression in the primary tumor was an independent marker of prolonged over all survival. As a tool to facilitate clinical biomarker studies the Human Protein Atlas has created a tissue dictionary as an introduction to human histology and histopathology. In Paper II this work is introduced.

A cancer diagnosis can be a complex process with difficulties of establishing tumor type in localized disease or organ of origin in generalized disease. Immunohistochemically assisted diagnosis of cancer is common practice among pathologists where its application combined with known protein expression profiles of different cancer types, can strengthen or help dismiss a suspected diagnosis. In Paper III the diagnostic performance of 27 commonly used antibodies are tested in a predominantly metastatic, multicancer cohort using TMA technique. Overall these 27 diagnostic markers showed a low sensitivity and specificity for its intended use, highlighting the need for novel, more specific markers.

Breast, ovarian, endometrial and ovarian cancers affect predominantly women. Differential diagnostics between these cancer types can be challenging. In Paper IV an algorithm, based on six different IHC markers, to differentiate between these cancer types is presented. A new diagnostic marker for breast cancer, namely ZAG is also introduced.

In Paper V the transcriptomic landscape of the adrenal gland is explored by combining a transcriptomic approach with a immunohistochemistry based proteomic approach. In the adrenal gland we were able to detect 253 genes with an elevated pattern of expression in the adrenal gland, as compared to 31 other normal human tissue types analyzed. This combination of a transcriptomic and immunohistochemical approach provides a foundation for a deeper understanding of the adrenal glands function and physiology.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2017. 43 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1294
Keyword
Cancer, biomarkers, differential diagnostics, immunohistochemistry, transcriptomics, protein profiling, adrenal gland.
National Category
Basic Medicine
Research subject
Pathology
Identifiers
urn:nbn:se:uu:diva-312939 (URN)978-91-554-9802-3 (ISBN)
Public defence
2017-03-10, Fåhraeussalen, Rudbecklaboratoriet, Dag Hammarskjölds v 20, Uppsala, 09:00 (English)
Opponent
Supervisors
Available from: 2017-02-17 Created: 2017-01-16 Last updated: 2017-02-17

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Gremel, GabrielaBergman, JuliaDjureinovic, DijanaEdqvist, Per-HenrikHellberg, DanMicke, PatrickPontén, Fredrik

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Gremel, GabrielaBergman, JuliaDjureinovic, DijanaEdqvist, Per-HenrikHellberg, DanMicke, PatrickPontén, Fredrik
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Molecular and Morphological PathologyScience for Life Laboratory, SciLifeLabCenter for Clinical Research DalarnaDepartment of Women's and Children's Health
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