Improving the efficacy of targeted trials by multiple-marker analysis in castration-resistant prostate cancer.
OBJECTIVE
In order to improve the efficacy of targeted therapy trials, the expression profiles of several molecular markers that are potential candidates for targeted therapy were analyzed in patients with progressive castration-resistant prostate cancer.


METHODS
Paraffin-embedded samples of tumor tissue from 51 patients obtained from biopsies of metastases or remaining prostates were analyzed immunohistochemically for the expression of EGFR, PDGFRβ, Her-2/neu, c-Kit, and VEGF. Staining was analyzed according to the percentage of positively stained tumor cells and the intensity of staining.


RESULTS
According to the different cut-off values of 10%, 30%, 50%, or 70% for the percentage of positively stained cells, different rates of expression were found. Expression rates ranged from 30.6% to 61.2% for EGFR, from 34.7% to 57.1% for PDGFRβ, from 9.6% to 28.8% for Her-2/neu, from 12.5% to 22.4% for c-Kit, and from 51.1% to 74.5% for VEGF. Defining positive expression as ≥ 30% positively stained tumor cells, with an intensity of staining of ≥ 2+, resulted in positive expression of EGFR in 38.8%, PDGFRβ in 24.5%, Her-2/neu in 13.5%, c-Kit in 6.4%, and VEGF in 44.7% of the patients.


CONCLUSIONS
Our results demonstrate simultaneous expression of several markers in castration-resistant prostate cancer tissue. Translation of the results into modern, multi-arm clinical trial designs will improve the efficacy of recruiting and obtaining results, compared with multiple double-arm trials.
Ohlmann
Carsten-Henning
CH
Division of Urologic Oncology, Department of Urology, University of Cologne, Cologne, Germany. Carsten.Ohlmann@uks.eu
Markert
Eva
E
Gerharz
Michael
M
Dienes
Hans-Peter
HP
Stöckle
Michael
M
Engelmann
Udo
U
Heidenreich
Axel
A
D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D002986:Clinical Trials as Topic; D016503:Drug Delivery Systems; D066246:ErbB Receptors / Q000096:biosynthesis; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009919:Orchiectomy; D018579:Patient Selection; D011471:Prostatic Neoplasms / Q000378:metabolism*; D019009:Proto-Oncogene Proteins c-kit / Q000096:biosynthesis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000096:biosynthesis; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis
D014408:Biomarkers, Tumor; D066246:ErbB Receptors; D019009:Proto-Oncogene Proteins c-kit; D018719:Erb-b2 Receptor Tyrosine Kinases; D020797:Receptor, Platelet-Derived Growth Factor beta; D042461:Vascular Endothelial Growth Factor A; C512478:EGFR protein, human; C508053:ERBB2 protein, human