Use of p53 in the diagnosis of upper-tract transitional cell carcinoma

Objectives. To assess the usefulness of p53 staining of cytology specimens obtained ureteroscopically in the diagnosis of upper-tract transitional cell carcinoma (TCC). Methods. We collected specimens from 43 patients undergoing a total of 50 ureteroscopic procedures for a variety of indications, including the diagnosis of TCC. Specimens were obtained by direct biopsy with forceps or basket whenever possible. We examined specimens for evidence of TCC by cytospin as well as cell block for any visible fragments. Each specimen was then stained for overexpression of p53 by immunohistochemical staining, and the degree of staining was graded. Eight patients subsequently underwent nephroureterectomy; the pathologic specimens were stained for p53 and compared with the cytology results. Results. Staining for p53 was positive in specimens from 36 of 50 procedures, including all 28 with ureteroscopic or cytologic evidence of TCC (P <0.0001). By contrast, cytology accurately diagnosed only 23 of the 28. Specimens from all 14 procedures that were negative also stained negative for p53. Specimens from all 8 procedures with no tumor seen and atypical cytology stained positive for p53; 4 of 5 patients with adequate follow-up have had a tissue diagnosis of TCC at that site. Overall, 35 of the 36 specimens that stained positive for p53 were obtained from patients with some history of TCC (P <0.0001). No significant association could be found between degree of staining and grade (P = 0.3034). The degree of staining of ureteroscopic biopsy specimens was identical to that of the nephroureterectomy specimen in 6 of 8 cases. Conclusions. p53 nuclear protein staining of cytology specimens obtained ureteroscopically appears to correlate well with the presence of upper-tract urinary TCC. Further study is needed to determine if it can provide a definitive diagnosis in cases with indeterminate cytologic findings.