Expression of Ki-67 and COX-2 in patients with upper urinary tract urothelial carcinoma.

OBJECTIVES: To investigate the prognostic value of Ki-67, cyclooxygenase-2 (COX-2), E-cadherin, and retinoblastoma protein (pRB) in patients with urothelial carcinoma of the upper urinary tract.

METHODS: From January 1998 to December 2005, the specimens from 107 patients with urothelial carcinoma of the upper urinary tract who had undergone nephroureterectomy were analyzed. The expression of Ki-67, COX-2, E-cadherin, and pRB was examined by immunochemistry on tissue microarray sections. The correlation of the immunoreactivity with the pathologic parameters and progression-free and cancer-specific survival were examined.

RESULTS: Ki-67 and COX-2 were overexpressed in 26 (24%) and 38 patients (36%), respectively. The loss of E-cadherin expression was observed in 66 patients (62%). Altered pRB expression was found in 37 patients (34%). Overexpression of Ki-67 (P = .041 and P = .006, respectively) and COX-2 (P = .002 and P = .001, respectively) was associated with the pathologic stage and grade. Multivariate analysis showed that Ki-67 overexpression (P = .002), T stage (P = .009), and lymph node metastases (P = .009) were independent predictors of progression-free survival. In addition, Ki-67 overexpression (P = .007) and pathologic T stage (P = .003) were independent predictors of cancer-specific survival. No association was found between the pathologic findings and prognosis and the other markers (E-cadherin and pRB).

CONCLUSIONS: Our results suggest that Ki-67 overexpression is an independent predictor of the progression of urothelial carcinoma of the upper urinary tract. Patients with Ki-67 overexpression should be followed up more closely. In addition, they might be candidates for future prospective therapy trials.