Three‐dimensional microscopic analysis of clinical prostate specimens

Royen, Martin E. van; Verhoef, Esther I.; Kweldam, Charlotte F.; Cappellen, Wiggert A. van; Kremers, Gert‐Jan; Houtsmuller, Adriaan B.; Leenders, Geert J.L.H. van

doi:10.1111/his.13022

Cited by 74 publications

(81 citation statements)

References 23 publications

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“…The Gleason grading system underwent further specifications, orchestrated by the International Society of Urological Pathology (ISUP), that aimed to standardize current practice which, over the years, had begun to deviate from the original description by Donald Gleason [24,25,26]. Despite all efforts, it must be said that the interobserver variability of this powerful grading system was, and remains, moderate, and that further work is necessary to harmonize the human perception of morphological patterns [27,28,29], or support it with computer-assisted analysis [30,31]. Alternatively, molecular markers may come to our aid to improve our classification of prostate cancer.…”

Section: Spatial and Morphological Heterogeneity Of Prostate Cancermentioning

confidence: 99%

“…The genetic mechanisms are relatively well-understood, but the relationship between the clones and their spatial distribution are not clear. Some insights could be acquired from the most recent study on the architecture of prostate cancer [31], which showed that prostate cancer comprises a complex integrative structure of intercommunicating tubules. This implies that, regionally at least, there is an epithelial continuity of all the structural elements (glands).…”

Section: Genetic/molecular Heterogeneitymentioning

confidence: 99%

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The Heterogeneity of Prostate Cancer: A Practical Approach

Tolkach¹,

Kristiansen²

2018

Pathobiology

101

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Prostate cancer is a paradigm tumor model for heterogeneity in almost every sense. Its clinical, spatial, and morphological heterogeneity divided by the high-level molecular genetic diversity outline the complexity of this disease in the clinical and research settings. In this review, we summarize the main aspects of prostate cancer heterogeneity at different levels, with special attention given to the spatial heterogeneity within the prostate, and to the standard morphological heterogeneity, with respect to tumor grading and modern classifications. We also cover the complex issue of molecular genetic heterogeneity, discussing it in the context of the current evidence of the genetic characterization of prostate carcinoma; the interpatient, intertumoral (multifocal disease), and intratumoral heterogeneity; tumor clonality; and metastatic disease. Clinical and research implications are summarized and serve to address the most pertinent problems stemming from the extreme heterogeneity of prostate cancer.

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Section: Spatial and Morphological Heterogeneity Of Prostate Cancermentioning

confidence: 99%

Section: Genetic/molecular Heterogeneitymentioning

confidence: 99%

The Heterogeneity of Prostate Cancer: A Practical Approach

Tolkach¹,

Kristiansen²

2018

Pathobiology

101

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“…In addition, Van Royen et al using BABB clearing could further apply immuno-histochemistry to cleared prostate biopsies followed by confocal microscopy. Of interest, the authors note that the cleared specimens retained a high DNA yield and could further be subjected to a polymerase chain reaction [42]. The extent of tissue clearing techniques application towards the field of cancer is not limited to its clinical applications.…”

Section: What the Future Holdsmentioning

confidence: 99%

Neuroscience in the third dimension: shedding new light on the brain with tissue clearing

2017

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For centuries analyses of tissues have depended on sectioning methods. Recent developments of tissue clearing techniques have now opened a segway from studying tissues in 2 dimensions to 3 dimensions. This particular advantage echoes heavily in the field of neuroscience, where in the last several years there has been an active shift towards understanding the complex orchestration of neural circuits. In the past five years, many tissue-clearing protocols have spawned. This is due to varying strength of each clearing protocol to specific applications. However, two main protocols have shown their applicability to a vast number of applications and thus are exponentially being used by a growing number of laboratories. In this review, we focus specifically on two major tissue-clearing method families, derived from the 3DISCO and the CLARITY clearing protocols. Moreover, we provide a “hands-on” description of each tissue clearing protocol and the steps to look out for when deciding to choose a specific tissue clearing protocol. Lastly, we provide perspectives for the development of tissue clearing protocols into the research community in the fields of embryology and cancer.

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“…Das Gleason-Graduierungssystem erfuhr weitere Verfeinerungen, die von der International Society of Urological Pathology (ISUP) zusammengetragen und beschrieben wurden, um die derzeitige Praxis, die im Laufe der Jahre von der ursprünglichen Beschreibung von Donald Gleason abgewichen war, zu beschreiben und zu standardisieren [24][25][26]. Trotz aller Bemühungen muss gesagt werden, dass die Untersucherübereinstimmung auch dieses prognostisch mächtigen Graduierungssystems nur moderat war und bleibt, und dass weitere Arbeit notwendig ist, um die menschliche Wahrnehmung morphologischer Muster zu harmonisieren [27][28][29] oder durch computergestützte Analyse zu unterstützen [30,31]. Alternativ kön-nen uns künftig vielleicht molekulare Marker dabei helfen, unsere Klassifikation des Prostatakrebses zu verbessern.…”

Section: Morphologische Heterogenitätunclassified

“…Die genetischen Mechanismen sind relativ gut verstanden, aber die Beziehung zwischen den Klonen und ihre räumliche Verteilung sind nicht klar. Einige Erkenntnisse konnten aus der jüngsten Studie über die Architektur des Prostatakrebses gewonnen werden [31], die zeigte, dass der Prostatakrebs eine komplexe integrative Struktur von interkommunizierenden Tubuli umfasst. Dies impliziert, dass zumindest regional eine epitheliale Kontinuität aller Strukturelemente (Drüsen) besteht.…”

Section: Ein Kurzer üBerblick üBer Die Genetik Des Prostatakrebsesunclassified

Die Heterogenität des Prostatakrebses: Ein praxisorientierter Ansatz

Tolkach¹,

Kristiansen²

2018

Kompass Onkol

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Prostatakrebs ist in nahezu jeder Hinsicht ein beispielhaftes Tumormodell für Heterogenität. Seine klinische, räumliche und morphologische Heterogenität, dividiert durch die hochgradige molekular-genetische Diversität, umreißt die Komplexität dieses Krankheitsbildes im Klinik- und Forschungsumfeld. In dem vorliegenden Review fassen wir die Hauptaspekte der Heterogenität des Prostatakrebses auf verschiedenen Ebenen zusammen, unter besonderer Berücksichtigung der räumlichen Heterogenität innerhalb der Prostata sowie der morphologischen Standardheterogenität in Bezug auf Tumor-Grading und moderne Klassifikationen. Wir befassen uns auch mit der komplexen Frage der molekulargenetischen Heterogenität und diskutieren sie im Zusammenhang mit den aktuellen Erkenntnissen zur genetischen Charakterisierung von Prostatakarzinomen, mit der Heterogenität zwischen Patienten und Tumoren (multifokale Erkrankung) sowie der Heterogenität innerhalb eines Tumors, mit der Tumorklonalität und mit der Metastasierung. Die möglichen Konsequenzen für Klinik und Forschung werden zusammengefasst und dazu verwendet, die relevantesten Probleme zu diskutieren, die sich aus der extremen Heterogenität des Prostatakrebses ergeben. Übersetzung aus Tolkach Y, Kristiansen G: Pathobiology 2018;85:108-116.

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Three‐dimensional microscopic analysis of clinical prostate specimens

Abstract: In conclusion, the applicability of 3D imaging to archival FFPE and fresh clinical specimens offers unlimited opportunities to study clinical and biological topics of interest in their actual 3D context.

Cited by 74 publications

References 23 publications

The Heterogeneity of Prostate Cancer: A Practical Approach

The Heterogeneity of Prostate Cancer: A Practical Approach

Neuroscience in the third dimension: shedding new light on the brain with tissue clearing

Die Heterogenität des Prostatakrebses: Ein praxisorientierter Ansatz

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