BACKGROUND: Molecular signatures in cancer tissue may be useful for diagnosis 
and are associated with survival. We used results from high-density tissue 
microarrays (TMAs) to define combinations of candidate biomarkers associated 
with the rate of prostate cancer progression after radical prostatectomy that 
could identify patients at high risk for recurrence.
METHODS: Fourteen candidate biomarkers for prostate cancer for which antibodies 
are available included hepsin, pim-1 kinase, E-cadherin (ECAD; cell adhesion 
molecule), alpha-methylacyl-coenzyme A racemase, and EZH2 (enhancer of zeste 
homolog 2, a transcriptional repressor). TMAs containing more than 2000 tumor 
samples from 259 patients who underwent radical prostatectomy for localized 
prostate cancer were studied with these antibodies. Immunohistochemistry results 
were evaluated in conjunction with clinical parameters associated with prostate 
cancer progression, including tumor stage, Gleason score, and prostate-specific 
antigen (PSA) level. Recurrence was defined as a postsurgery PSA level of more 
than 0.2 ng/mL. All statistical tests were two-sided.
RESULTS: Moderate or strong expression of EZH2 coupled with at most moderate 
expression of ECAD (i.e., a positive EZH2:ECAD status) was the biomarker 
combination that was most strongly associated with the recurrence of prostate 
cancer. EZH2:ECAD status was statistically significantly associated with 
prostate cancer recurrence in a training set of 103 patients (relative risk [RR] 
= 2.52, 95% confidence interval [CI] = 1.09 to 5.81; P =.021), in a validation 
set of 80 patients (RR = 3.72, 95% CI = 1.27 to 10.91; P =.009), and in the 
combined set of 183 patients (RR = 2.96, 95% CI = 1.56 to 5.61; P<.001). 
EZH2:ECAD status was statistically significantly associated with disease 
recurrence even after adjusting for clinical parameters, such as tumor stage, 
Gleason score, and PSA level (hazard ratio = 3.19, 95% CI = 1.50 to 6.77; P 
=.003).
CONCLUSION: EZH2:ECAD status was statistically significantly associated with 
prostate cancer recurrence after radical prostatectomy and may be useful in 
defining a cohort of high-risk patients.