ErbB3, Cyclin D1 and Ki67 nuclear staining predicts biochemical recurrence in prostate cancer treated by radical prostatectomy

Abstract

10096 Background: The nuclear accumulation of growth factor receptor was reported to be associated to increased cell proliferation. Cyclin D1 and Ki67 are nuclear markers of cell proliferation. Deregulation of Cyclin D1 and Ki67 expression play a role in tumorigenesis and metastasis. Recently, we observed that nuclear localization of ErbB3 was associated with prostate cancer progression. The objective of this study was to determine if the association of cell proliferation markers and nuclear localization of ErbB3 could predict biochemical recurrence (BCR) in patients with prostate cancer following radical prostatectomy. Methods: Using immunohistochemistry we analyzed a tissue microarray containing 386 cores from 64 formalin-fixed paraffin embedded specimens from prostate cancer patients who had undergone radical prostatectomy. No patient had received hormone therapy prior to surgery and prior to BCR. Antibodies against Cyclin D1, ErbB3 and Ki67 proteins were used. Results: Nuclear staining was 60%, 67% and 86% for Cyclin D1, ErbB3 and Ki67 respectively. In our cohort, 29 of 64 PCa patients (45%) had a BCR after a median 3 years of follow-up. Thirty seven (37) percent of patients had positive nuclear staining for all three markers. BCR free survival probability at 3 years was not significant for each marker individually, except for ErbB3 in positive surgical margin patients. When all three markers were combined for nuclear staining Kaplan-Meier analysis BCR free was 0.4 and 0.1 for positive and negative nuclear staining respectively (p=0.0068). Univariate COX regression analysis shows a 2.98 fold (95% CI: 1.29 - 6.86, p=0.01) higher rate of BCR in patients positive for these three markers. In addition, in a multivariate model, including pre-operative PSA (p=0.19), pathologic stage (p=0.29), Gleason grade (p=0.40) and specimens that had positive nuclear staining for the 3 markers were associated with a 3.97 fold higher rate of BCR (95% CI: 1.54 - 10.25, p=0.0068). Conclusion: These results suggest that the association of cell proliferation markers and nuclear localization of ErbB3 could be useful in predicting recurrence following radical prostatectomy and guide therapeutic decisions. Large scale trials are needed to confirm these results. No significant financial relationships to disclose.