Expression of Cyclooxygenase-2 in Normal Urothelium, and Superficial and Advanced Transitional Cell Carcinoma of Bladder

Vitaly Margulis, Shahrokh F. Shariat, Raheela Ashfaq, Melissa Thompson, Arthur I Sagalowsky, Jer-Tsong Hsieh, Yair Lotan

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)1163-1168
Number of pages6
JournalJournal of Urology
Volume177
Issue number3
DOIs
StatePublished - Mar 2007

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Urothelium
Transitional Cell Carcinoma
Cyclooxygenase 2
Urinary Bladder
Cystectomy
Lymph Nodes
Cyclin D1
Neoplasm Metastasis
Urinary Bladder Neoplasms
Caspase 3
Recurrence
Cyclin E
Oncogenes
Multivariate Analysis
Staining and Labeling

Keywords

  • bladder
  • bladder neoplasms
  • carcinoma
  • cyclooxygenase 2
  • mortality
  • transitional cell

ASJC Scopus subject areas

  • Urology

Cite this

Expression of Cyclooxygenase-2 in Normal Urothelium, and Superficial and Advanced Transitional Cell Carcinoma of Bladder. / Margulis, Vitaly; Shariat, Shahrokh F.; Ashfaq, Raheela; Thompson, Melissa; Sagalowsky, Arthur I; Hsieh, Jer-Tsong; Lotan, Yair.

In: Journal of Urology, Vol. 177, No. 3, 03.2007, p. 1163-1168.

Research output: Contribution to journalArticle

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abstract = "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.",
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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

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.

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