High KI67 expression is associated, in a multi-variate model, with lower risk of biochemical recurrence in prostate cancer patients following radical prostatectomy

Abstract

21112 Background: The prediction of disease progression in prostate cancer patients following radical prostatectomy (RP) remains problematic. The use of molecular markers could offer a better stratification of patients more at risk of progression. As such, we recently reported that nuclear ErbB3 was associated with Gleason score and hormone-refractory status. The objective of this study was to evaluate whether ErbB3 could predict overall biochemical recurrence (BCR). In addition, we evaluated if three nuclear markers known to be associated with progression (Cyclin D1, Ki67 and androgen receptor) were more significant predictors of BCR than ErbB3 alone or in combination. Methods: Using immunohistochemistry, we analyzed a tissue microarray containing 373 cores from 63 RP specimens. No patient had received hormone therapy prior to surgery and prior to BCR. The quantitative analysis of nuclear staining was measured by two independent observers (ErbB3, Cyclin D1 and AR) or with the ImagePro Plus softwareTM (Ki67). Marker expressions were categorized as either positive or negative according to the median expression. Results: Of the four markers analyzed, Ki67 alone was the strongest predictor of overall BCR. In a multi-variate Cox regression model (backward conditional), while controlling for the pre-operative PSA, Gleason score and lymph node invasion at time of surgery, KI67 was found to be an independent predictor of BCR with a KI67+ patients having lower risk of BCR (HR=-2.51, p=0.015, CI 95%: 1.19–5.29). We then analyzed if different marker combinations could predict BCR. Patients positive for nuclear AR or AR+/Cyclin D1+ double positive were found to have lower risk of BCR (Kaplan-Meier, p=0.047 and p=0.026, respectively). However, in the multi- variate model, the combinations of Cyclin D1+/AR+ (HR=-2.28, p=0.053, CI 95%: 0.94–5.49), ErbB3+/Ki67+ (HR=-2.43, p=0.034, CI 95%: 1.07- 5.52) and AR+/Ki67+ (HR=-2.32, p=0.049, CI 95%: 1.01–5.35) could not improve on the predictive value of KI67 alone. Conclusions: The major new finding of the study is that patients positive for KI67 expression were at a lower risk of developing BCR, which contrast previously published results, and warrants further investigations. No significant financial relationships to disclose.