Format

Send to

Choose Destination
Prostate Cancer Prostatic Dis. 2016 Sep;19(3):264-70. doi: 10.1038/pcan.2016.12. Epub 2016 May 3.

Prognostic value of Ki67 in localized prostate carcinoma: a multi-institutional study of >1000 prostatectomies.

Author information

1
University of Washington, Seattle, WA, USA.
2
MD Anderson Cancer Center, Houston, TX, USA.
3
Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
4
Canary Foundation, Redwood City, CA, USA.
5
Cleveland Clinic, Cleveland, OH, USA.
6
University of British Columbia, Vancouver, BC, Canada.
7
University of California at San Francisco, CA, USA.
8
Eastern Virginia Medical School, Norfolk, VA, USA.
9
University of Texas Health Sciences Center at San Antonio, TX, USA.
10
Stanford University, Stanford, CA, USA.

Abstract

BACKGROUND:

Expanding interest in and use of active surveillance for early state prostate cancer (PC) has increased need for prognostic biomarkers. Using a multi-institutional tissue microarray resource including over 1000 radical prostatectomy samples, we sought to correlate Ki67 expression captured by an automated image analysis system with clinicopathological features and validate its utility as a clinical grade test in predicting cancer-specific outcomes.

METHODS:

After immunostaining, the Ki67 proliferation index (PI) of tumor areas of each core (three cancer cores/case) was analyzed using a nuclear quantification algorithm (Aperio). We assessed whether Ki67 PI was associated with clinicopathological factors and recurrence-free survival (RFS) including biochemical recurrence, metastasis or PC death (7-year median follow-up).

RESULTS:

In 1004 PCs (∼4000 tissue cores) Ki67 PI showed significantly higher inter-tumor (0.68) than intra-tumor variation (0.39). Ki67 PI was associated with stage (P<0.0001), seminal vesicle invasion (SVI, P=0.02), extracapsular extension (ECE, P<0.0001) and Gleason score (GS, P<0.0001). Ki67 PI as a continuous variable significantly correlated with recurrence-free, overall and disease-specific survival by multivariable Cox proportional hazard model (hazards ratio (HR)=1.04-1.1, P=0.02-0.0008). High Ki67 score (defined as ⩾5%) was significantly associated with worse RFS (HR=1.47, P=0.0007) and worse overall survival (HR=2.03, P=0.03).

CONCLUSIONS:

In localized PC treated by radical prostatectomy, higher Ki67 PI assessed using a clinical grade automated algorithm is strongly associated with a higher GS, stage, SVI and ECE and greater probability of recurrence.

PMID:
27136741
PMCID:
PMC5536893
DOI:
10.1038/pcan.2016.12
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center