Prognostic correlation of cell cycle progression score and Ki-67 as a predictor of aggressiveness, biochemical failure, and mortality in men with high-risk prostate cancer treated with external beam radiation therapy
Abstract
Objectives
Ki-67 is a proliferation marker in prostate cancer. A prognostic RNA signature was developed to characterize prostate cancer aggressiveness.
The aim was to evaluate prognostic correlation of CCP and Ki-67 with biochemical failure (BF), and survival in high-risk prostate cancer patients (pts) treated with radiation therapy (RT).
Methods
CCP score and Ki-67 were derived retrospectively from pre-treatment paraffin-embedded prostate cancer tissue of 33 men diagnosed from 2002 to 2006.
CCP score was calculated as an average expression of 31 CCP genes. Ki-67 was determined by IHC. Single pathologist evaluated all tissues. Factors associated to failure and survival were analyzed.
Results
Median CCP score was 0.9 (-0-1 – 2.6). CCP 0: 1 pt; CCP 1: 19 pts; CCP 2: 13 pts. Median Ki-67 was 8.9. Ki-67 cutpoint was 15.08%.
BF and DSM were observed in 21% and 9%. Ki-67[[ce:hsp sp="0.25"/]]≥[[ce:hsp sp="0.25"/]]15% predicted BF (p[[ce:hsp sp="0.25"/]]=[[ce:hsp sp="0.25"/]]0.043). With a median follow-up of 8.4 years, 10-year BF, OS, DM and DSM for CCP 1 vs. CCP 2 was 76–71% (p[[ce:hsp sp="0.25"/]]=[[ce:hsp sp="0.25"/]]0.83), 83–73% (p[[ce:hsp sp="0.25"/]]=[[ce:hsp sp="0.25"/]]0.86), 89–85% (p[[ce:hsp sp="0.25"/]]=[[ce:hsp sp="0.25"/]]0.84), and 94–78% (p[[ce:hsp sp="0.25"/]]=[[ce:hsp sp="0.25"/]]0.66).
On univariate, high Ki-67 was correlated with BF (p[[ce:hsp sp="0.25"/]]=[[ce:hsp sp="0.25"/]]0.013), OS (p[[ce:hsp sp="0.25"/]]=[[ce:hsp sp="0.25"/]]0.023), DM (p[[ce:hsp sp="0.25"/]]=[[ce:hsp sp="0.25"/]]0.007), and DSM (p[[ce:hsp sp="0.25"/]]=[[ce:hsp sp="0.25"/]]0.01). On Cox MVA, high Ki-67 had a BF trend (p[[ce:hsp sp="0.25"/]]=[[ce:hsp sp="0.25"/]]0.063). High CCP score was not correlated with DSM.
Conclusions
High Ki-67 significantly predicted outcome and provided prognostic information. CCP score may improve accuracy stratification. We did not provide prognostic correlation of CCP and DSM. It should be validated in a larger cohort of pts.
Keywords: ptsIHCHECCPADTFFbFOSGUGICTCv3.0CTVDFSDMFSCSSPCaPSAGyRTProstate cancerBiomarkersCCP genesKi-67