Relations of p53, ki-67, bcl-2 and p27kip1 expressions with grading systems and prognosis in transitional cell carcinomas of the bladder

Objectives: There is a need for other prognostic markers for TCCs of the bladder as grade&stage seem to fall short in many cases. Our aim was (1) to evaluate the value of several grading systems, namely, modified Bergkvist (MB), Murphy, and WHO/ISUP; (2) to investigate the relationship of some of the biologic prognostic parameters with clinical outcome. Materials - Methods: p53, Ki-67, bcl-2 and p27Kip1 immunohistochemical staining was performed on 78 cases (97 TUR/14 radical cystectomy). Results: All grading systems were found to correlate with stage&clinical outcome (dead or alive) (p<0,01), and MB system had significant correlation with recurrence, too (p<0,05). There was a significant correlation of Ki-67 with grade&stage: The expression of this marker increased progressively from MB grade I (6.5%) to IIA (18.1%), IIB (22%), III (39.9%), to IV (45.2%) (p<0,01) and from TA (19.8%), to T1(25.1%), T2(34%), and to T3(41.5). Furthermore, Ki-67 positivity was significantly lower in cases that survived longer than 24 months (n=32), compared to those who had died of disease within 2 years (n=13, mean survival 11.4 months) (p<0,05). bcl-2 had inverse correlation with the stage (p<0,05). p27Kip1 had inverse correlation with MB grade (p<0.05). There was also a trend for p27Kip1 to decrease as the stage increased (TA vs T2, p=0.057; T1 vs T2, p=0.046; TA vs T3, p=0.021; T1 vs T3, p=0.01). Conclusions: In this study, all grading systems were found to have good prognostic value. MB system was also good in predicting recurrence. This may be related to the number of subgroups in this classification system. Among the biological markers tested, Ki-67 proved to be an independent factor correlating with the grade of the tumor. Moreover, Ki-67 expression also appears to have significant prognostic value, and may, therefore, be utilized as an adjunct to grade&stage in predicting the clinical outcome.