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

Abstract

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.

• Authors: F Huber, M Montani, T Sulser, R Jaggi, P Wild, H Moch, H Gevensleben, M Schmid, S Wyder, G Kristiansen
• Journal: British journal of cancer (Br J Cancer) Vol. 112 Issue 1 Pg. 140-8 (Jan 06 2015) ISSN: 1532-1827 [Electronic] England
• PMID: 25422912 (Publication Type: Journal Article)

Chemical References

• Biomarkers, Tumor

Topics

• Aged
• Biomarkers, Tumor (analysis)
• Cohort Studies
• Disease Progression
• Humans
• Immunohistochemistry
• Male
• Middle Aged
• Multivariate Analysis
• Prognosis
• Proportional Hazards Models
• Prostatic Neoplasms (chemistry)