Expression of Cyclin D1 in Transitional Cell Carcinoma of the Urinary Bladder

Choi, Young Deuk; Park, Young Nyun; Hong, Joo Eui; Hong, Sung Joon

Abstract

PURPOSE: Cyclin D1 plays critical roles in the progression of cells through the G1 phase of the cell cycle, which has been implicated as a putative protooncogene, while p53 protein affects different phase checkpoint pathways in the normal cell cycle, which mutations occur in poor prognosis of cancer. We attempted to determine their significance for tumor behavior and prognosis of transitional cell carcinoma(TCCa) of the bladder in human.
MATERIALS AND METHODS
Formalin fixed-paraffin embedded tissue specimens from 102 patients with TCCa of the urinary bladder were examined. Nuclear expression was detected by immunohistochemical analysis with a standard avidin-biotin immunoperoxidase method, using the monoclonal antibody cyclin D1 and p53(DO7).
RESULTS
Cyclin D1 and p53 protein immunostaining of the nucleus was observed in 49 tumors(48.0%) and 55 tumors(53.9%) respectively. Overexpression of cyclin D1 showed significant inverse correlation with the histological grade and significant correlation with recurrence. Overexpression of p53 protein showed a significant correlation with the histological grade and stage(p<0.01). 65.3% (32 out of 49 tumors), of the cyclin D1 positive tumors exhibited expression for p53 protein(p<0.05). Patients with TCCa coexpressing cyclin D1 and p53 protein had a significantly poorer prognosis than those expressing neither cyclin D1 nor p53 protein(p<0.001).
CONCLUSIONS
Cyclin D1 in bladder TCCa is closely related to early tumor differentiation and associated with recurrence. Simultaneous overexpression of both cyclin D1 and p53 protein is related to more aggressive tumor behavior and poorer prognosis. This indicates that cyclin D1 evaluation may be a further useful element for selecting subgroup of patients who should be treated with more aggressive therapies.