SIGNIFICANCE OF CYCLIN D1 OVEREXPRESSION IN TRANSITIONAL-CELL CARCINOMAS OF THE URINARY-BLADDER AND ITS CORRELATION WITH HISTOPATHOLOGIC FEATURES

BACKGROUND. Genetic alterations leading to neoplastic transformation o f the urothelium are Likely to involve the activation of oncogenes and loss of functional tumor suppressor genes. Cyclin D1 has been implica ted as a putative protooncogene whereas mutations of the p53 gene occu r frequently in invasive transitional cell carcinomas (TCCs) of the ur inary bladder. In dris study, cyclin D1 overexpression and nuclear acc umulation of p53 were evaluated and the results correlated with histop athologic features. METHODS. TCCs of the urinary bladder from 161 surg ical procedures were evaluated for cyclin D1 overexpression and nuclea r accumulation of p53. Results were correlated with tumor grade, T cla ssification, and papillary status. Topologic distributions of cyclin D 1, p53, and proliferating cellular nuclear antigen (PCNA) were evaluat ed. Northern blot analysis was performed on selected specimens. RESULT S. 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. App roximately 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 t he TCCs beyond TI was immunoreactive. Overexpression of cyclin D1 was observed only in papillary type TCCs. Results of Northern blot analysi s for cyclin D1 were comparable to those of immunohistochemistry. CONC LUSIONS. The observed significant relation between cyclin D1 overexpre ssion and tumor grade/T classification suggests that cyclin DI may be a useful biologic marker for biopsied materials or urine cytology spec imens, The prognostic significance of cyclin D1 overexpression in TCCs remains to be determined. (C) 1997 American Cancer Society.