Format

Send to

Choose Destination
Microarrays (Basel). 2014 Apr 17;3(2):137-58. doi: 10.3390/microarrays3020137.

Qualitative and Quantitative Requirements for Assessing Prognostic Markers in Prostate Cancer.

Author information

1
Institute of Pathology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany. cburdelski@uke.de.
2
Institute of Pathology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany. matuszewska.aleksandra@yahoo.de.
3
Institute of Pathology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany. m.kluth@uke.de.
4
Institute of Pathology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany. c.koop@uke.de.
5
General, Visceral and Thoracic Surgery Department and Clinic, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany. k.grupp@uke.de.
6
Institute of Pathology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany. s.steurer@uke.de.
7
Institute of Pathology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany. c.wittmer@uke.de.
8
Institute of Pathology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany. s.minner@uke.de.
9
Institute of Pathology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany. m.tsourlakis@uke.de.
10
Institute of Pathology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany. g.sauter@uke.de.
11
Martini-Clinic, Prostate Cancer Center, Martinistr. 52, 20246, Hamburg, Germany. tschlomm@uke.de.
12
Department of Urology, Section for Translational Prostate Cancer Research, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany. tschlomm@uke.de.
13
Institute of Pathology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany. r.simon@uke.de.

Abstract

Molecular prognostic markers are urgently needed in order to improve therapy decisions in prostate cancer. To better understand the requirements for biomarker studies, we re-analyzed prostate cancer tissue microarray immunohistochemistry (IHC) data from 39 prognosis markers in subsets of 50 - >10,000 tumors. We found a strong association between the "prognostic power" of individual markers and the number of tissues that should be minimally included in such studies. The prognostic relevance of more than 90% of the 39 IHC markers could be detected if ≥6400 tissue samples were analyzed. Studying markers of tissue quality, including immunohistochemistry of ets-related gene (ERG) and vimentin, and fluorescence in-situ hybridization analysis of human epidermal growth factor receptor 2 (HER2), we found that 18% of tissues in our tissue microarray (TMA) showed signs of reduced tissue preservation and limited immunoreactivity. Comparing the results of Kaplan-Meier survival analyses or associations to ERG immunohistochemistry in subsets of tumors with and without exclusion of these defective tissues did not reveal statistically relevant differences. In summary, our study demonstrates that TMA-based marker validation studies using biochemical recurrence as an endpoint require at least 6400 individual tissue samples for establishing statistically relevant associations between the expression of molecular markers and patient outcome if weak to moderate prognosticators should also be reliably identified.

KEYWORDS:

marker validation; number of samples; prognosis; prostate cancer; tissue microarray; tissue quality

Supplemental Content

Full text links

Icon for Multidisciplinary Digital Publishing Institute (MDPI) Icon for PubMed Central
Loading ...
Support Center