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Genetische Marker und Prognosefaktoren beim Prostatakarzinom

Molecular biomarkers and prognostic factors for prostate cancer

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Zusammenfassung

In der Ära der personalisierten Medizin werden große Hoffnungen in neu etablierte genetische Biomarker gesetzt, um die prognostische Lücke aus klinischen und histopathologischen Parametern bei der Therapie und Risikostratifizierung des Prostatakarzinoms zu schließen. In der vorliegenden Arbeit werden prognostische und prädiktive genetische Biomarker vorgestellt, die klinische Relevanz bei Diagnosestellung und nach einer definitiven Therapie des Prostatakarzinoms haben. Hierbei werden Grundsätze der Biomarkerforschung erläutert und die aktuelle Studienlage bezüglich des Progensa-PCA3-Tests, der TMPRSS2:ERG-Genfusion sowie des ConfirmMDx- und des Prolaris-Tests, des OncotypeDX Genomic Prostate Score und des Decipher Classifier präsentiert. Die Evidenz hat sich in den vergangenen Jahren stark verbessert. Nichtsdestotrotz besteht weiterhin ein Mangel an großen, multizentrischen und v. a. prospektiven Validierungsstudien. Darüber hinaus existieren keine komparativen Studien.

Abstract

In the era of personalized medicine and precision oncology, innovative genetic biomarkers are of emerging interest to close the diagnostic and prognostic gap that is left by current clinicopathologic risk classifiers. The current review article summarizes evidence regarding prognostic and predictive genetic biomarkers that are currently in widespread clinical use at initial diagnosis as well as following definitive treatment of prostate cancer. We give a brief summary about basic principles of biomarker research studies and present current data for the Progensa PC3 test, TMPRSS2:ERG gene fusion, ConfirmMDx, Prolaris gene panel, OncotypeDX Genomic Prostate score, and Decipher classifier. Evidence regarding those genetic biomarkers has heavily increased recently. However, there is still a lack of large, multicentric and prospective clinical validation studies. Furthermore, comparative studies that investigate the prognostic value of various genetic biomarkers are needed.

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Authors and Affiliations

  1. Urologische Klinik und Poliklinik, Klinikum der Universität München, Ludwig-Maximilians-Universität, Marchioninistr. 15, 81377, München, Deutschland

    A. Kretschmer

  2. Institut für Pathologie, Universitätsklinikum Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Deutschland

    Y. Tolkach & G. Kristiansen

  3. Klinik und Poliklinik für Urologie und Kinderurologie, Universitätsklinikum Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Deutschland

    J. Ellinger

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  1. A. Kretschmer
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  3. J. Ellinger
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  4. G. Kristiansen
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Correspondence to A. Kretschmer.

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Interessenkonflikt

A. Kretschmer, Y. Tolkach, J. Ellinger und G. Kristiansen geben an, dass kein Interessenkonflikt besteht.

Dieser Beitrag beinhaltet keine von den Autoren durchgeführten Studien an Menschen oder Tieren.

Additional information

Redaktion

M.-O. Grimm, Jena

A. Gross, Hamburg

C.-G. Stief, München

J.-U. Stolzenburg, Leipzig

in Zusammenarbeit mit

der Akademie

der Deutschen Urologen

CME-Fragebogen

CME-Fragebogen

Welche Antwort ist richtig? Welcher der folgenden Tests ist ein Urintest?

ConfirmMDx (MDx Health, Irvine, USA)

Oncotype DX Genomic Prostate Score (Genomic Health, Redwood City, USA)

Decipher (GenomeDX, Vancouver, Kanada)

Prostate Cancer Antigen 3 (Progensa, Bedford, USA)

Prolaris (Myriad Genetics Inc., Salt Lake City, USA)

Welche Antwort ist richtig? Der Prolaris-Test (Myriad Genetics Inc., Salt Lake City, USA) beruht auf der Messung einer Gensignatur, die für welchen der folgenden zellbiologischen Prozesse bedeutsam ist?

Glukosemetabolismus

Lipolyse

Zellzyklusregulation

Phosphotidyl-3-Kinase/AKT-System

Chemotaxis

Welche Antwort ist richtig? Welcher der folgenden Gewebetests basiert auf Proteomics?

ConfirmMDx (MDx Health, Irvine, USA)

Oncotype DX Genomic Prostate Score (Genomic Health, Redwood City, USA)

Decipher (GenomeDX, Vancouver, Kanada)

ProMark (Metamark, Cambridge, USA)

Prolaris (Myriad Genetics Inc., Salt Lake City, USA)

Die Interpretation von welchem der folgenden molekularen Biomarkertests basiert auf dem sog. GPS-Score?

ConfirmMDx (MDx Health, Irvine, USA)

Oncotype DX Genomic Prostate Score (Genomic Health, Redwood City, USA)

Decipher (GenomeDX, Vancouver, Kanada)

Prostate Cancer Antigen 3 (Progensa, Bedford, USA)

Prolaris (Myriad Genetics Inc., Salt Lake City, USA)

Welche Antwort ist richtig? Welcher Biomarker beruht auf der Detektion von Deletionen oder Additionen einzelner Chromosomen?

ConfirmMDx (MDx Health, Irvine, USA)

Oncotype DX Genomic Prostate Score (Genomic Health, Redwood City, USA)

Decipher (GenomeDX, Vancouver, Kanada)

DNA-Ploidie

Prolaris (Myriad Genetics Inc., Salt Lake City, USA)

Welche Antwort ist richtig? Eine Aneuploidie wird heutzutage in der Regel mittels welcher Methode detektiert?

Polymerasekettenreaktion (PCR)

Southern Blot

Durchflusszytometrie

Cellsearch®-System

Hämatoxylin-Eosin(HE)-Färbung

Welche Antwort ist richtig? Der ConfirmMDx (MDx Health, Irvine, USA) untersucht welche molekulare Veränderung?

Hypermethylierung

Deletion

Punktmutation

Addition

Frameshift-Mutation

Welche Antwort ist richtig? Wie häufig tritt die TMPRSS2:ERG-Genfusion bei Prostatakarzinomen auf?

Ca. 5 %

Ca. 20 %

Ca. 50 %

Ca. 80 %

Ca. 100 %

Welche Antwort ist richtig? Bei welchem molekularen Biomarkertest handelt es sich um ein molekulares Korrelat einer Proliferationsmessung am Tumorgewebe?

ConfirmMDx (MDx Health, Irvine, USA)

Oncotype DX Genomic Prostate Score (Genomic Health, Redwood City, USA)

Decipher (GenomeDX, Vancouver, Kanada)

Prostate Cancer Antigen 3 (Progensa, Bedford, USA)

Prolaris (Myriad Genetics Inc., Salt Lake City, USA)

Welche Antwort ist richtig? Vor welchem molekularen Biomarkertest ist eine digital-rektale Prostatamassage obligat?

ConfirmMDx (MDx Health, Irvine, USA)

Oncotype DX Genomic Prostate Score (Genomic Health, Redwood City, USA)

Decipher (GenomeDX, Vancouver, Kanada)

Prostate Cancer Antigen 3 (Progensa, Bedford, USA)

Prolaris (Myriad Genetics Inc., Salt Lake City, USA)

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Kretschmer, A., Tolkach, Y., Ellinger, J. et al. Genetische Marker und Prognosefaktoren beim Prostatakarzinom. Urologe 56, 933–944 (2017). https://doi.org/10.1007/s00120-017-0418-0

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