Significance of cyclin D1 overexpression in transitional cell carcinomas of the urinary bladder and its correlation with histopathologic features.

Abstract

Genetic alterations leading to neoplastic transformation of the urothelium are likely to involve the activation of oncogenes and loss of functional tumor suppressor genes. Cyclin D1 has been implicated as a putative protooncogene whereas mutations of the p53 gene occur frequently in invasive transitional cell carcinomas (TCCs) of the urinary bladder. In this study, cyclin D1 overexpression and nuclear accumulation of p53 were evaluated and the results correlated with histopathologic features. TCCs of the urinary bladder from 161 surgical procedures were evaluated for cyclin D1 overexpression and nuclear accumulation of p53. Results were correlated with tumor grade, T classification, and papillary status. Topologic distributions of cyclin D1, p53, and proliferating cellular nuclear antigen (PCNA) were evaluated. Northern blot analysis was performed on selected specimens. Overexpression of cyclin D1 was observed in 47% (24 of 51) of Grade 1 TCCs and 20% (13 of 65) of Grade 2 TCCs but in no Grade 3 TCCs. Approximately 34% (14 of 41) of Ta classified TCCs and 21% (13 of 63) of T1 classified TCCs were immunoreactive for cyclin D1 whereas none of the TCCs beyond T1 was immunoreactive. Overexpression of cyclin D1 was observed only in papillary type TCCs. Results of Northern blot analysis for cyclin D1 were comparable to those of immunohistochemistry. The observed significant relation between cyclin D1 overexpression and tumor grade/T classification suggests that cyclin D1 may be a useful biologic marker for biopsied materials or urine cytology specimens. The prognostic significance of cyclin D1 overexpression in TCCs remains to be determined.