p53 Protein and Ki-67 Overexpression in Urothelial Dysplasia of Bladder

Mutated tumor suppression gene p53 is a common genetic abnormality in most papillary or invasive transitional cell carcinomas (TCC). In these cases, overexpression of p53 protein is detectable in nuclei by immunohistochemical methods. Nuclear antigen Ki-67, a marker of cellular proliferation, has been shown to correlate with the growth of many human neoplasms, including TCC. Since overexpression of p53 protein and increased Ki-67 proliferative activity have been a consistent finding in TCC, p53 and Ki-67 expression may be used as markers of urothelial cells with significant genetic alterations. In this study, the authors have investigated whether there is increased p53 and Ki-67 expression in varying grades of urothelial dysplasia. Staining for p53 and Ki-67 using formalin-fixed, paraffin-embedded sections was performed using a Dako Autostainer, followed by counting positive cells using an automatic cellular imaging system (ACIS). The high-grade dysplasia/CIS group (n = 16) had a similar high percentage and intensity of p53 staining (45.3 +/- 4.3%; 28.2 +/- 6.1 arbitrary units [AU]) as the TCC group (n = 16. 53.6 +/- 3.9%; 36.8 +/- 5.7 AU), but revealed a significantly higher percentage and intensity of p53 staining than the low-grade dysplasia (n = 14, 25.6 +/- 3.3%; 12.2 +/- 2.0 AU) and benign group (n = 10, 10.0 +/- 3.3%; 5.8 +/- 1.7 AU). Percentage of p53-positive cells counted by ACIS was similar to that obtained by manual counting. In addition, expression of Ki-67 in all four groups paralleled p53 expression. The authors' data showing overexpression of p53 and Ki-67 in high-grade urothelial dysplasia/CIS similar to that observed in TCC support the notion that high-grade urothelial dysplasia/CIS is a precursor of invasive TCC.