Cyclin Dl expression in TCC of the bladder: Correlation with WAF1, p53 and Ki67

Introduction: In the normal cell cycle, cyclin Dl is essential for Gl/S phase transition. Wild-type p53 strongly induces expression of the WAF1 gene and the resulting p21wafl protein binds and inactivates the cyclin/cdk complexes. Our aim was to investigate cyclin Dl expression in TCC of the bladder and correlate these results with the expression of W API, p53 and K167. Materials and methods: Paraffin sections of tumours from 150 patients (35 women and 115 men, mean age 68 years, range 41-91; TalTl in 97, T2-4 in 53: Gl in 20, G2 in 73 and G3 in 57) were stained for cyclin Dl using standard immunohistochemistry. The proportion of positively staining tumour cells was recorded. A representative subset of tumours was also stained for Ki67 and all tumours had previously been stained for p53 and WAF1. Results: The median value for cyclin Dl staining was significantly higher in Ta/Tl tumours (41%) than in T2-4 tumours (8%, P < 0.005); moreover, the median value for cyclin Dl staining was significantly higher in Gl/2 tumours (43%) than in G3 tumours (14%, P < 0.005). There was a very strong correlation between cyclin Dl and WAFI expression (P < 0.001) but no correlation with p53. Ki67 expression was significantly associated with increasing tumour stage (P < 0.005) and histological grade (P < 0.05) but did not correlate with cyclin Dl expression. Conclusions: Cyclin Dl expression is significantly higher in low-stage, well-differentiated bladder tumours and strongly correlates with WAFI expression. Further studies are necessary to assess the functional significance of this relationship and to determine the clinical relevance of cyclin Dl in bladder cancer. © 1998 British Journal of Urology.