Overexpression of cyclin D1 is associated with metastatic prostate cancer to bone

Cyclin D1 is a key regulator of the G₁ phase progression of the cell cycle. There is increasing evidence that deregulated cyclin D1 expression is implicated in tumorigenesis and tumor progression in certain neoplasms. Recently, it has been reported that cyclin D1 overexpression might be related to the evolution of androgen-independent disease in prostate cancer. This study was conducted to investigate patterns of cyclin D1 expression in prostate cancer samples representing different points in the natural history and treatment evolution of the disease. Association with clinical outcomes was also explored. Using immunohistochemistry, 86 radical prostatectomy specimens (53 naive and 33 after androgen deprivation) and 22 androgen- independent bone metastases were studied. We examined the difference in cyclin D1 expression in primary versus metastatic cases. In addition, we examined the association in primary cases between cyclin D1 expression and clinicopathological parameters of poor clinical outcome, including time to prostate-specific antigen relapse and Ki67 proliferative index. Cyclin D1- positive phenotype, defined as identification of positive immunoreactivity in the nuclei of ≥20% of tumor cells, was observed in 10 of 86 (11%) primary cases compared with 15 of 22 (68%) androgen-independent bone metastases (P = 0.001). There was no correlation between cyclin D1 overexpression and either Gleason score, neo-adjuvant hormone treatment, or prostate-specific antigen relapse. We observed a statistical association between cyclin D1 overexpression and high Ki67 proliferative index, defined as ≥20% of positive tumor cells (P = 0.02). These data support the hypothesis that cyclin D1 overexpression may represent an oncogenic event in androgen- independent metastatic prostate cancer to the bone.