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Cha, Cho, Yim, Cho, Hong, Cho, Kim, Ahn, and Kim: Correlation of Cyclooxygenase-2 Expression and Microvessel Density with Prognosis in Transitional Cell Carcinoma of the Upper Urinary Tract
Original Article

Korean J Urol 2007;48(4):376-382.

Published online: 18 December 2007

DOI: https://doi.org/10.4111/kju.2007.48.4.376

Correlation of Cyclooxygenase-2 Expression and Microvessel Density with Prognosis in Transitional Cell Carcinoma of the Upper Urinary Tract

Min Ho Cha, Dae Sung Cho, Hyunee Yim1, Kang Su Cho2, Sung Joon Hong2, Nam Hoon Cho3, Sun Il Kim, Hyun Soo Ahn, Se Joong Kim

1Pathology, Ajou University School of Medicine, Suwon

2Departments of Urology College of Medicine, Seoul, Kore

3Departments of Pathology, Yonsei University College of Medicine, Seoul, Korea

4From the Departments of Urology

Corresponding author: Kim Se-joong Department of Urology, Ajou University Hospital San Won-dong, Yeongtong-gu, Suwon-si, Gyeonggi-do 5 443-721 TEL: 031-219-5272 FAX: 031-219-5276 E-mail: sejoong@ajou.ac.kr

Received 15 January 2007       Accepted 2 March 2007

Copyright © 2007 The Korean Urological Association

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Purpose:

The aim of this study was to investigate the relationship of cyclooxygenase (CoX)-2 expression and microvessel density (MVD), a reflection of angiogenesis, with prognosis in patients with transitional cell carcinoma of the upper urinary tract (TCC-UUT).

Materials and Methods:

Formalin-fixed, paraffin-embedded tissue sections of TCC-UUT from 91 patients, who had undergone radical nephroureterectomy, were examined immunohistochemically using antibodies against CoX-2 and CD34. MVD was determined with CD34-stained slides. The expression patterns of COX-2 and MVD were compared with the clinicopathological variables.

Results:

The COX-2 expression was significantly correlated with T stage (p=0.002), N stage (p=0.010), and grade (p=0.027). MVD was also significantly correlated with T stage (p く 0.001), N stage (p=0.002), and grade (p=0.001). The COX-2 expression was significantly correlated with MVD (p=0.001). The survival rate of patients with COX-2 positive tumors or high MVD was significantly lower than that of patients with COX-2 negative tumors or low MVD, respectively (p=0.0013, p=0.0312). Univariate analyses identified T stage, N stage, grade, COX-2 expression, and MVD as significant prognostic factors for cancer-specific survival; multivariate analyses indicated that T stage was the only independent prognostic factor.

Conclusions:

The increased expression of COX-2 and MVD is associated with a worse prognosis in TCC-UUT. The COX-2 expression is correlated with MVD. These results suggest that COX-2 may play an important role in the progression of TCC-UUT and angiogenesis may be affected by COX-2 during the progression of TCC-UUT.

Keywords: Cyclooxygenase 2, Prognosis, Transitional cell carcinoma, Urinary tract

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Fig. 1.
Immunohistochemical staining for cyclooxygenase-2 (COX-2) in transitional cell carcinoma of the upper urinary tract tissues (x400). (A) Cancer cells are not stained (COX-2 intensity 0). (B) Smooth muscle cells are stained as an internal control. Cancer cells are stained weakly compared to an internal control (intensity 1). (C) Cancer cells are stained in same intensity as internal control (intensity 2). (D) Cancer cells are strongly stained for COX-2 (intensity 3).
kju-48-376f1.tif
Fig. 2.
Kaplan-Meier cancer-specific survival curves according to cyclooxygenase-2 (COX-2) expression (A) or microvessel density (MVD) (B). The survival rate of patients with COX-2 positive tumors or high MVD was significantly lower than that of patients with COX-2 negative tumors or low MVD, respectively (p=0.0013, p=0.0312).
kju-48-376f2.tif
Table 1.
Clinicopathological data
Characteristics No. of patients (%)
T stage  
 Ta 8 (8.8)
 T1 51 (56.0)
 T2 9 (9.9)
 T3 19 (20.9)
 T4 4 (4.4)
N stage  
 N0 84 (92.3)
 N1 5 (5.5)
 N2 2 (2.2)
Grade  
 Low 36 (39.6)
 High 55 (60.4)
Tumor location  
 Renal pelvis 50 (54.9)
 Ureter 41 (45.1)
Previous history of bladder cancer  
 No 84 (92.3)
 Yes 7 (7.7)
Coexisting bladder cancer  
 No 83 (91.2)
 Yes 8 (8.8)
Bladder cancer recurrence  
 No 58 (63.7)
 Yes 33 (36.3)
Table 2.
Relationship between COX-2 expression or microvessel density and clinicopathological variables
Variables No. of patients (%) p-value∗ MVD p-value†
COX-2 (-) COX-2 (+)
T stage          
 Superficial (Ta+T1) 53 (89.8) 6 (10.2) 0.002 44.56 ±19.34 <0.001
 Invasive (T2-T4) 20 (62.5) 12 (37.5)   83.03 ±28.20  
N stage          
 N0 70 (83.3) 14 (16.7) 0.010 55.42 ±25.65 0.002
 N1+N2 3 (42.9) 4(57.1)   90.14 ±49.45  
Grade          
 Low 33 (91.7) 3 (8.3) 0.027 45.75 ±22.69 0.001
 High 40 (72.7) 15 (27.3)   66.16 ±30.42  
Tumor location          
 Renal pelvis 43 (86.0) 7 (14.0) 0.126 63.08 ±34.22 0.060
 Ureter 30 (73.2) 11 (26.8)   52.00 ±20.57  
Previous history of bladder cancer          
 No 66 (78.6) 18(21.4) 0.171 58.50 ±29.93 0.644
 Yes 7(100) 0 (0)   53.14 ±20.55  
Coexisting bladder cancer          
 No 67 (80.7) 16 (19.3) 0.698 58.81 ±30.13 0.453
 Yes 6 (75.0) 2 (25.0)   50.63 ±17.49  
Bladder cancer recurrence          
 No 49 (84.5) 9 (15.5) 0.176 58.50 ±31.47 0.860
 Yes 24 (72.7) 9 (27.3)   57.36 ±25.37  

COX-2: cyclooxygenase-2, MVD: microvessel density. ∗: analyzed by chi-square test, † analyzed by independent-sample t-test.

Table 3.
Univariate and multivariate survival analyses
Variables Univariate∗ Multivariate†
p-value Hazards ratio p-value
T stage 0.0001 4.164 0.010
N stage 0.0343 1.171 0.802
Grade 0.0352 1.431 0.551
Tumor location 0.9235 1.017 0.972
Previous history of bladder cancer 0.3867 2.230 0.287
Coexisting bladder cancer 0.7075 1.310 0.694
Bladder cancer recurrence 0.5185 1.276 0.569
COX-2 0.0013 2.360 0.091
MVD 0.0312 0.716 0.588

COX-2: cyclooxygenase-2, MVD: microvessel density. ∗: analyzed by log-rank test, †: analyzed by COX proportional hazards regression model.

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