Qualitative and Quantitative Requirements for Assessing Prognostic Markers in Prostate Cancer

Microarrays

Christoph Burdelski³  Aleksandra Matuszewska³  Martina Kluth³  Christina Koop³  Katharina Grupp¹  Stefan Steurer³  Corinna Wittmer³  Sarah Minner³  Maria Christina Tsourlakis³  Guido Sauter³  Thorsten Schlomm² 

[1] General, Visceral and Thoracic Surgery Department and Clinic, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany; E-Mail:;Martini-Clinic, Prostate Cancer Center, Martinistr. 52, 20246, Hamburg, Germany; E-Mail:;Institute of Pathology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany; E-Mails:

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

DOI  :  10.3390/microarrays3020137

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.