Relationship of genetic instability with immunoreactivities for p53 protein and proliferating cell nuclear antigen in transitional cell carcinoma of the bladder

Objective: To elucidate the relationship between genetic instability and tumor development in transitional cell carcinoma (TCC) of the bladder. Methods: The genetic instability as assessed by 2c deviation index (2cDI) and 5c exceeding rate (ScER) was compared with immunoreactivities for p53 protein and proliferating cell nuclear antigen (PCNA) in specimens obtained from 65 patients with primary untreated TCCs. Results: Both p53 and PCNA immunoreactivities significantly correlated with histological grade as well as stage. The immunoreactivity of p53 significantly correlated with that of PCNA, while a dissociation of the positive correlation between p53 immunoreactivity and PCNA expression was noted in the TCCs with high 2cDI value (greater than or equal to 22.0) and/or high 5cER(greater than or equal to 10%). In addition, PCNA expression became higher as the genetic instability increased, however, the p53 immunoreactivity was not parallel with the change of genetic instability. Moreover, some TCCs with high genetic instability (2cDI greater than or equal to 2.0 and 5cERr greater than or equal to 10%) showed concomitant expression of high PCNA and low p53 protein, whose clinical outcome was poor in general. Conclusions: The inactivation of p53 may represent a rather early event in the development of TCC of the bladder. However, the proliferative activity in itself rather than the effect due to a specific alteration in p53 plays an important role in the development and progression in TCC of the bladder.