Comprehensive validation of published immunohistochemical prognostic biomarkers of prostate cancer-what has gone wrong? A blueprint for the way forward in biomarker studies

Huber, F; Montani, Matteo; Sulser, T; Jaggi, Rolf; Wild, P; Moch, H; Gevensleben, H; Schmid-Maurer, Christine; Wyder, Stefan; Kristiansen, G (2015). Comprehensive validation of published immunohistochemical prognostic biomarkers of prostate cancer-what has gone wrong? A blueprint for the way forward in biomarker studies. British journal of cancer, 112(1), pp. 140-148. Nature Publishing Group 10.1038/bjc.2014.588

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BACKGROUND Treatment planning of localised prostate cancer remains challenging. Besides conventional parameters, a wealth of prognostic biomarkers has been proposed so far. None of which, however, have successfully been implemented in a routine setting so far. The aim of our study was to systematically verify a set of published prognostic markers for prostate cancer. METHODS Following an in-depth PubMed search, 28 markers were selected that have been proposed as multivariate prognostic markers for primary prostate cancer. Their prognostic validity was examined in a radical prostatectomy cohort of 238 patients with a median follow-up of 60 months and biochemical progression as endpoint of the analysis. Immunohistochemical evaluation was performed using previously published cut-off values, but allowing for optimisation if necessary. Univariate and multivariate Cox regression were used to determine the prognostic value of biomarkers included in this study. RESULTS Despite the application of various cut-offs in the analysis, only four (14%) markers were verified as independently prognostic (AKT1, stromal AR, EZH2, and PSMA) for PSA relapse following radical prostatectomy. CONCLUSIONS Apparently, many immunohistochemistry-based studies on prognostic markers seem to be over-optimistic. Codes of best practice, such as the REMARK guidelines, may facilitate the performance of conclusive and transparent future studies.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Forschungsbereich Pathologie > Forschungsgruppe Molekularbiologie
04 Faculty of Medicine > Service Sector > Institute of Pathology
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR)
04 Faculty of Medicine > Service Sector > Institute of Pathology > Clinical Pathology

UniBE Contributor:

Montani, Matteo; Jaggi, Rolf; Schmid-Maurer, Christine and Wyder, Stefan

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

0007-0920

Publisher:

Nature Publishing Group

Language:

English

Submitter:

Doris Haefelin

Date Deposited:

20 Feb 2015 16:41

Last Modified:

07 Jan 2016 07:44

Publisher DOI:

10.1038/bjc.2014.588

PubMed ID:

25422912

BORIS DOI:

10.7892/boris.63542

URI:

https://boris.unibe.ch/id/eprint/63542

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