Quantifying the Ki-67 Heterogeneity Profile in Prostate Cancer

73 Background: Ki-67 is a robust predictive/prognostic marker in prostate cancer however tumor heterogeneity may compromise its clinical utility when Ki-67 is determined off of prostate biopsy samples. We examined the variation of Ki-67 in prostate biopsy samples by NCCN risk groups and the location of the highest Ki-67 relative to the most dominant lesion on multiparametric (MP) MRI. METHODS An IRB approved retrospective analysis was done on 77 consecutive men whose prostate biopsies revealed cancer. Using a MRI/US fusion device (Artemis), biopsy cores were obtained systematically and when MRI indicated a lesion, by targeting. Ki-67 staining was determined by a manual semi-quantitative method and reported as % of positive cells. The highest Ki-67 per patient was used to determine inter-prostatic variation. Ki-67 range (highest Ki-67 minus lowest Ki-67 value) was used to determine intra-prostatic variation on a subset of 47 patients with ≥2 positive biopsy cores. Ki-67 range was also used to evaluate intra-lesion variation on 31 MP MRI defined lesions with > 1 targeted positive biopsy core. The relationship of the dominant lesion (lesion with the largest tumor diameter) to the highest Ki-67 in the entire prostate was examined for 10 patients with ≥2 distinct lesions on MP MRI. Analysis of variance (ANOVA) was used to evaluate differences between the means of NCCN-defined risk groups. RESULTS Inter-prostatic Ki-67 mean±standard deviation (SD) values for low, intermediate and high risk patients were 5.1% ± 3.8%, 7.4% ± 6.8%, and 12.0% ± 12.4% (ANOVA p=0.01). Intra-prostatic mean±SD Ki-67 ranges in low, intermediate, and high risk patients were 2.6% ± 3.4%, 4.6% ± 6.4%, 9.5% ± 10.6% (ANOVA p = 0.0246). Intra-lesion mean±SD Ki-67 ranges in low, intermediate and high risk patients were 1.0%±1.0%, 4.0%±4.29%, and 6.7%±11.51% (ANOVA p=0.39). The dominant lesion harbored the highest Ki-67 30% of the time. CONCLUSIONS High risk patients have significantly higher inter- and intra-prostatic Ki-67 heterogeneity profiles than men with low/intermediate risk disease. The highest Ki-67 is often not located in the dominant MRI defined lesion. This data can inform future biopsy strategies when integrating Ki-67 into clinical practice.