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Aktuelle Urol 2015; 46(02): 129-143
DOI: 10.1055/s-0034-1398544
Übersicht
© Georg Thieme Verlag KG Stuttgart · New York

Neue Biomarker im Serum und im Urin zur Detektion des Prostatakarzinoms

New Biomarkers in Serum and Urine for Detection of Prostate Cancer
C. Stephan
1   Klinik für Urologie, Charité – Universitätsmedizin Berlin
2   Berliner Forschungsinstitut für Urologie, Berlin
,
K. Jung
1   Klinik für Urologie, Charité – Universitätsmedizin Berlin
2   Berliner Forschungsinstitut für Urologie, Berlin
,
K. Miller
1   Klinik für Urologie, Charité – Universitätsmedizin Berlin
,
B. Ralla
1   Klinik für Urologie, Charité – Universitätsmedizin Berlin
› Author Affiliations
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Publication History

Publication Date:
21 April 2015 (online)

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Zusammenfassung

Das prostataspezifische Antigen (PSA) hat in den letzten 3 Jahrzehnten das Management des Prostatakarzinoms (PCa) revolutioniert. Dieser häufig genutzte Biomarker hat trotz der eindeutigen Korrelation zum PCa eine geringe Spezifität, sodass ein dringender Bedarf an neuen Tumormarkern besteht, die v. a. klinisch relevante und aggressive Formen des PCa nachweisen können. Von allen Serummarkern zeigt nur der 2012 von der FDA zugelassene [−2]proPSA-basierte sogenannte „Prostate Health Index“ Phi eine verbesserte Spezifität gegenüber dem PSA und dem prozentualen freien PSA (%fPSA). Andere Kallikreine im Serum oder auch Sarkosin im Serum und Urin zeigen unterschiedliche Ergebnisse und sollten deshalb eher zurückhaltend bezüglich einer verbesserten PCa-Detektion bewertet werden. Im Urin hat der ebenfalls 2012 von der FDA zugelassene mRNA-basierte Urinmarker „Prostate Cancer Gene 3“ (PCA3) nachgewiesen, dass v. a. bei Wiederholungsbiopsien eine verbesserte diagnostische Genauigkeit im Vergleich zum PSA und %fPSA möglich ist. Allerdings gibt es beim PCA3 eine ungenügende diagnostische Sensitivität bei hohen Werten als auch eine fehlende Korrelation zur Tumoraggressivität. Die Entdeckung der TMPRSS2:ETS-Genfusionen im Jahr 2005, welche im Gewebe von etwa 50% aller PCa-Patienten auftreten, war ein Meilenstein in der Forschung des Prostatakarzinoms. Der auf der Plattform des PCA3 basierende Urintest für TMPRSS2:ETS zeigte allerdings nur in Kombination mit dem PCA3 eine verbesserte diagnostische Effizienz. Im direkten Vergleich der beiden besten derzeit verfügbaren Tumormarker sind Phi und PCA3 als gleichwertig anzusehen.

Abstract

Prostate-specific antigen (PSA) has revolutionized the management of prostate cancer (PCa) within the last 3 decades. This widely used tumour marker strongly correlates with the risk of harbouring a PCa but it lacks specificity. Therefore there is an urgent need for new biomarkers especially to detect clinically significant and aggressive PCa. Of all PSA-based markers, only the FDA-approved prostate health index phi shows improved specificity over percent free (%fPSA) and total PSA. Other serum kallikreins or sarcosine in serum or urine show more ambiguous data. In urine, the FDA-approved prostate cancer gene 3 (PCA3) has also proven its utility in the detection and management of early PCa with advantages as compared with PSA and %fPSA. However, some aspects of its correlation with aggressiveness and the low sensitivity at very high values have to be re-examined. The detection of alterations of the androgen regulated TMPRSS2 and ETS transcription factor genes in tissue of ~50% of all PCa patients was a milestone in PCa research. But only the combination of the urinary assays for TMPRSS2:ERG gene fusion and PCA3 (both use the same platform) show the expected improved accuracy for PCa detection. Comparisons of phi and PCA3, the best available PCa biomarkers so far, show an equal performance of both parameters.

Schlüsselwörter

Prostatakarzinom - Diagnostik - PSA - Biomarker

Key words

prostate cancer - diagnosis - PSA - biomarkers

Editorial Comment

 

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