Expression of Ki-67 and COX-2 in patients with upper urinary tract urothelial carcinoma.
OBJECTIVE
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.
Jeon
Hwang Gyun
HG
Department of Urology, CHA Bundang Medical Center, CHA University, Seongnam, Korea.
Jeong
In Gab
IG
Bae
Jungbum
J
Lee
Jeong Woo
JW
Won
Jae-Kyung
JK
Paik
Jin Ho
JH
Kim
Hyeon Hoe
HH
Lee
Sang Eun
SE
Lee
Eunsik
E
D000328:Adult; D000368:Aged; D015820:Cadherins / Q000096:biosynthesis; D002295:Carcinoma, Transitional Cell / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000096:biosynthesis*; D007680:Kidney Neoplasms / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D016160:Retinoblastoma Protein / Q000096:biosynthesis; D014516:Ureteral Neoplasms / Q000378:metabolism*
D015820:Cadherins; D019394:Ki-67 Antigen; D016160:Retinoblastoma Protein; D051546:Cyclooxygenase 2