Prognostic value of nuclear versus cytoplasmic cyclin D1 in human prostate cancer.

Cyclin D1 (CCND1) as a regulator of the cell cycle has been implicated in disease progression and prognosis of human malignancies. However, its prognostic significance in cytoplasmic versus nuclear localizations has not been well established in human prostate cancer (PCa). We used 640 PCa cases with radical prostatectomy to build tissue microarrays. Normal prostate tissue and index tumor were cored in triplicate (0.6 mm). Slides were immunostained and then digitized. Spearman-test was used for correlations between CCND1 expression, clinicopathological variables, and biological markers. Kaplan-Meier, logrank, and Cox proportional hazard tests were used to evaluate the prognostic value of CCND1. The CCND1 expression index was higher in PCa compared to normal prostate for nuclear and cytoplasmic CCND1. Increased nuclear CCND1 in PCa was associated with preoperative PSA and Gleason scores. High expression of nuclear CCND1 was correlated with increased expression of MKI67, p-Akt, PIM2, p-FKHR, MYC, and SKP2. High levels of cytoplasmic CCND1 were correlated with increased p-Akt, PIM2, and MYC. Increased nuclear expression of CCND1 was associated with biochemical recurrence in PCa. Cytoplasmic expression was not. Our data suggested that expression of nuclear CCND1 was associated with clinopathological and biological markers that are involved in proliferation and survival in PCa. Cytoplasmic CCND1 shared some of these findings, but they were less statistically significant. These findings provide evidence that increased CCND1 promotes proliferation and facilitate disease progression, especially in the nucleus. Cyclin D1 might become a potential biomarker for the prediction of biochemical recurrence in PCa.