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.
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Acknowledgements
We cordially thank a large and dedicated Canary Foundation team of coordinating center staff, local coordinators, laboratory staff and physicians who have made this study possible. The study was supported by The Canary Foundation; the Department of Defense W81XWH-11-1-0380; the NCI Early Detection Research Network U01 CA086402, CA152737, CA08636815; P30 CA054174; and the Pacific Northwest Prostate Cancer SPORE P50 CA097186.
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Supplementary Information accompanies the paper on the Prostate Cancer and Prostatic Diseases website
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Tretiakova, M., Wei, W., Boyer, H. et al. Prognostic value of Ki67 in localized prostate carcinoma: a multi-institutional study of >1000 prostatectomies. Prostate Cancer Prostatic Dis 19, 264–270 (2016). https://doi.org/10.1038/pcan.2016.12
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DOI: https://doi.org/10.1038/pcan.2016.12
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