TY - JOUR
T1 - Expression of Cyclooxygenase-2 in Normal Urothelium, and Superficial and Advanced Transitional Cell Carcinoma of Bladder
AU - Margulis, Vitaly
AU - Shariat, Shahrokh F.
AU - Ashfaq, Raheela
AU - Thompson, Melissa
AU - Sagalowsky, Arthur I
AU - Hsieh, Jer-Tsong
AU - Lotan, Yair
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2007/3
Y1 - 2007/3
N2 - Purpose: We compared the differential expression of cyclooxygenase-2 in normal bladder tissue, primary bladder transitional cell carcinoma and transitional cell carcinoma metastases to lymph nodes, and determined whether cyclooxygenase-2 expression is associated with molecular alterations commonly found in bladder transitional cell carcinoma and clinical outcomes after radical cystectomy. Materials and Methods: Immunohistochemical staining for cyclooxygenase-2, survivin (Novus Biologicals, Littleton, Colorado), p21, p27, pRB, p53, MIB-1, Bax, Bcl-2, cyclin D1 (Dako™), cyclin E (Oncogene, Cambridge, Massachusetts) and caspase-3 (Cell Signaling, Beverley, Massachusetts) was performed on archival bladder specimens from 9 subjects who underwent cystectomy for benign causes, 21 patients who underwent transurethral resection and 157 consecutive patients after radical cystectomy, and on 41 positive lymph nodes. Results: Cyclooxygenase-2 was expressed in none of the 9 normal bladder specimens (0%), 52% of transurethral resection specimens, 62% of cystectomy specimens and 80% of lymph nodes involved with transitional cell carcinoma. Cyclooxygenase-2 expression was associated with higher pathological stage, lymphovascular invasion and metastases to lymph nodes (p = 0.001, 0.045 and 0.002, respectively). Cyclooxygenase-2 expression was associated with altered expression of p53 (p = 0.039), pRB (p = 0.025), cyclin D1 (p = 0.034) and caspase-3 (p = 0.014). On univariate analysis cyclooxygenase-2 expression was associated with an increased risk of disease recurrence and bladder cancer specific mortality (p = 0.0189 and 0.0472, respectively). However, on multivariate analysis only pathological stage and metastases to lymph nodes were associated with disease recurrence (p <0.001 and <0.001) and survival (p <0.001 and 0.015, respectively). Conclusions: Cyclooxygenase-2 is not expressed in normal bladder urothelium. Cyclooxygenase-2 over expression is associated with pathological and molecular features of biologically aggressive disease, suggesting a role for cyclooxygenase-2 in bladder cancer development and invasion.
AB - Purpose: We compared the differential expression of cyclooxygenase-2 in normal bladder tissue, primary bladder transitional cell carcinoma and transitional cell carcinoma metastases to lymph nodes, and determined whether cyclooxygenase-2 expression is associated with molecular alterations commonly found in bladder transitional cell carcinoma and clinical outcomes after radical cystectomy. Materials and Methods: Immunohistochemical staining for cyclooxygenase-2, survivin (Novus Biologicals, Littleton, Colorado), p21, p27, pRB, p53, MIB-1, Bax, Bcl-2, cyclin D1 (Dako™), cyclin E (Oncogene, Cambridge, Massachusetts) and caspase-3 (Cell Signaling, Beverley, Massachusetts) was performed on archival bladder specimens from 9 subjects who underwent cystectomy for benign causes, 21 patients who underwent transurethral resection and 157 consecutive patients after radical cystectomy, and on 41 positive lymph nodes. Results: Cyclooxygenase-2 was expressed in none of the 9 normal bladder specimens (0%), 52% of transurethral resection specimens, 62% of cystectomy specimens and 80% of lymph nodes involved with transitional cell carcinoma. Cyclooxygenase-2 expression was associated with higher pathological stage, lymphovascular invasion and metastases to lymph nodes (p = 0.001, 0.045 and 0.002, respectively). Cyclooxygenase-2 expression was associated with altered expression of p53 (p = 0.039), pRB (p = 0.025), cyclin D1 (p = 0.034) and caspase-3 (p = 0.014). On univariate analysis cyclooxygenase-2 expression was associated with an increased risk of disease recurrence and bladder cancer specific mortality (p = 0.0189 and 0.0472, respectively). However, on multivariate analysis only pathological stage and metastases to lymph nodes were associated with disease recurrence (p <0.001 and <0.001) and survival (p <0.001 and 0.015, respectively). Conclusions: Cyclooxygenase-2 is not expressed in normal bladder urothelium. Cyclooxygenase-2 over expression is associated with pathological and molecular features of biologically aggressive disease, suggesting a role for cyclooxygenase-2 in bladder cancer development and invasion.
KW - bladder
KW - bladder neoplasms
KW - carcinoma
KW - cyclooxygenase 2
KW - mortality
KW - transitional cell
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U2 - 10.1016/j.juro.2006.10.033
DO - 10.1016/j.juro.2006.10.033
M3 - Article
C2 - 17296438
AN - SCOPUS:33846807872
SN - 0022-5347
VL - 177
SP - 1163
EP - 1168
JO - Journal of Urology
JF - Journal of Urology
IS - 3
ER -