Association of tumor-associated trypsin inhibitor (TATI) expression with molecular markers, pathologic features and clinical outcomes of urothelial carcinoma of the urinary bladder

Oliver Patschan, Shahrokh F. Shariat, Daher C. Chade, Pierre I. Karakiewicz, Raheela Ashfaq, Yair Lotan, Kristina Hotakainen, Ulf Håkan Stenman, Anders Bjartell

Research output: Contribution to journalArticle

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Abstract

Purposes: To describe the differential tissue expression of tumor-associated trypsin inhibitor (TATI) in normal bladder urothelium, primary urothelial carcinoma of the bladder (UCB) and metastatic UCB and to assess the association of TATI expression with molecular markers commonly altered in UCB and clinical outcomes after radical cystectomy. Methods: Slides from eight cystectomy patients without cancer, 191 radical cystectomy patients, 20 lymph nodes without metastasis and 40 lymph nodes with UCB were stained. Tissue expression of TATI, cyclin E1, cyclin D1, p53, p21, p27, pRB, Ki-67, Bcl-2, Caspase-3, Survivin and Cyclooxigenase-2 was measured in a tissue microarray. Cancer-specific and recurrence-free survival after radical cystectomy was recorded. Results: TATI was expressed in 100% of patients without cancer, while 71% of radical cystectomy specimens and 90% of lymph node metastases exhibited decreased or no TATI expression. In radical cystectomy specimens, TATI expression decreased with advancing pathologic stage (P < 0. 001) and lymphovascular invasion (P = 0. 055). In univariate analyses, but not in multivariable Cox proportional hazard regression analyses, decreased TATI expression was associated with increased probability of tumor recurrence and cancer-specific mortality. Decreased TATI expression was correlated with altered expression of Cyclooxigenase-2 (P = 0. 005), p21 (P = 0. 035) and Ki-67 (P = 0. 004). Conclusions: We found that normal urothelium expresses TATI and that TATI expression decreases with advancing tumor stage. While there was no prognostic benefit to TATI when adjusted for standard clinicopathologic features, it seems to play an important biologic role in UCB pathogenesis and invasion. Its association with markers involved in the cell cycle, proliferation and inflammation serves as hypothesis for molecular interactions.

Original languageEnglish (US)
Pages (from-to)785-794
Number of pages10
JournalWorld Journal of Urology
Volume30
Issue number6
DOIs
StatePublished - Dec 2012

Fingerprint

Kazal Pancreatic Trypsin Inhibitor
Urinary Bladder
Carcinoma
Cystectomy
Urothelium
Neoplasms
Lymph Nodes
Neoplasm Metastasis
Recurrence
Cyclins
Cyclin D1
Caspase 3

Keywords

  • Bladder cancer
  • Cyclooxygenase-2
  • Cystectomy
  • KI67
  • p21
  • Recurrence
  • Survival
  • TATI

ASJC Scopus subject areas

  • Urology

Cite this

Association of tumor-associated trypsin inhibitor (TATI) expression with molecular markers, pathologic features and clinical outcomes of urothelial carcinoma of the urinary bladder. / Patschan, Oliver; Shariat, Shahrokh F.; Chade, Daher C.; Karakiewicz, Pierre I.; Ashfaq, Raheela; Lotan, Yair; Hotakainen, Kristina; Stenman, Ulf Håkan; Bjartell, Anders.

In: World Journal of Urology, Vol. 30, No. 6, 12.2012, p. 785-794.

Research output: Contribution to journalArticle

Patschan, Oliver ; Shariat, Shahrokh F. ; Chade, Daher C. ; Karakiewicz, Pierre I. ; Ashfaq, Raheela ; Lotan, Yair ; Hotakainen, Kristina ; Stenman, Ulf Håkan ; Bjartell, Anders. / Association of tumor-associated trypsin inhibitor (TATI) expression with molecular markers, pathologic features and clinical outcomes of urothelial carcinoma of the urinary bladder. In: World Journal of Urology. 2012 ; Vol. 30, No. 6. pp. 785-794.
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abstract = "Purposes: To describe the differential tissue expression of tumor-associated trypsin inhibitor (TATI) in normal bladder urothelium, primary urothelial carcinoma of the bladder (UCB) and metastatic UCB and to assess the association of TATI expression with molecular markers commonly altered in UCB and clinical outcomes after radical cystectomy. Methods: Slides from eight cystectomy patients without cancer, 191 radical cystectomy patients, 20 lymph nodes without metastasis and 40 lymph nodes with UCB were stained. Tissue expression of TATI, cyclin E1, cyclin D1, p53, p21, p27, pRB, Ki-67, Bcl-2, Caspase-3, Survivin and Cyclooxigenase-2 was measured in a tissue microarray. Cancer-specific and recurrence-free survival after radical cystectomy was recorded. Results: TATI was expressed in 100{\%} of patients without cancer, while 71{\%} of radical cystectomy specimens and 90{\%} of lymph node metastases exhibited decreased or no TATI expression. In radical cystectomy specimens, TATI expression decreased with advancing pathologic stage (P < 0. 001) and lymphovascular invasion (P = 0. 055). In univariate analyses, but not in multivariable Cox proportional hazard regression analyses, decreased TATI expression was associated with increased probability of tumor recurrence and cancer-specific mortality. Decreased TATI expression was correlated with altered expression of Cyclooxigenase-2 (P = 0. 005), p21 (P = 0. 035) and Ki-67 (P = 0. 004). Conclusions: We found that normal urothelium expresses TATI and that TATI expression decreases with advancing tumor stage. While there was no prognostic benefit to TATI when adjusted for standard clinicopathologic features, it seems to play an important biologic role in UCB pathogenesis and invasion. Its association with markers involved in the cell cycle, proliferation and inflammation serves as hypothesis for molecular interactions.",
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author = "Oliver Patschan and Shariat, {Shahrokh F.} and Chade, {Daher C.} and Karakiewicz, {Pierre I.} and Raheela Ashfaq and Yair Lotan and Kristina Hotakainen and Stenman, {Ulf H{\aa}kan} and Anders Bjartell",
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T1 - Association of tumor-associated trypsin inhibitor (TATI) expression with molecular markers, pathologic features and clinical outcomes of urothelial carcinoma of the urinary bladder

AU - Patschan, Oliver

AU - Shariat, Shahrokh F.

AU - Chade, Daher C.

AU - Karakiewicz, Pierre I.

AU - Ashfaq, Raheela

AU - Lotan, Yair

AU - Hotakainen, Kristina

AU - Stenman, Ulf Håkan

AU - Bjartell, Anders

PY - 2012/12

Y1 - 2012/12

N2 - Purposes: To describe the differential tissue expression of tumor-associated trypsin inhibitor (TATI) in normal bladder urothelium, primary urothelial carcinoma of the bladder (UCB) and metastatic UCB and to assess the association of TATI expression with molecular markers commonly altered in UCB and clinical outcomes after radical cystectomy. Methods: Slides from eight cystectomy patients without cancer, 191 radical cystectomy patients, 20 lymph nodes without metastasis and 40 lymph nodes with UCB were stained. Tissue expression of TATI, cyclin E1, cyclin D1, p53, p21, p27, pRB, Ki-67, Bcl-2, Caspase-3, Survivin and Cyclooxigenase-2 was measured in a tissue microarray. Cancer-specific and recurrence-free survival after radical cystectomy was recorded. Results: TATI was expressed in 100% of patients without cancer, while 71% of radical cystectomy specimens and 90% of lymph node metastases exhibited decreased or no TATI expression. In radical cystectomy specimens, TATI expression decreased with advancing pathologic stage (P < 0. 001) and lymphovascular invasion (P = 0. 055). In univariate analyses, but not in multivariable Cox proportional hazard regression analyses, decreased TATI expression was associated with increased probability of tumor recurrence and cancer-specific mortality. Decreased TATI expression was correlated with altered expression of Cyclooxigenase-2 (P = 0. 005), p21 (P = 0. 035) and Ki-67 (P = 0. 004). Conclusions: We found that normal urothelium expresses TATI and that TATI expression decreases with advancing tumor stage. While there was no prognostic benefit to TATI when adjusted for standard clinicopathologic features, it seems to play an important biologic role in UCB pathogenesis and invasion. Its association with markers involved in the cell cycle, proliferation and inflammation serves as hypothesis for molecular interactions.

AB - Purposes: To describe the differential tissue expression of tumor-associated trypsin inhibitor (TATI) in normal bladder urothelium, primary urothelial carcinoma of the bladder (UCB) and metastatic UCB and to assess the association of TATI expression with molecular markers commonly altered in UCB and clinical outcomes after radical cystectomy. Methods: Slides from eight cystectomy patients without cancer, 191 radical cystectomy patients, 20 lymph nodes without metastasis and 40 lymph nodes with UCB were stained. Tissue expression of TATI, cyclin E1, cyclin D1, p53, p21, p27, pRB, Ki-67, Bcl-2, Caspase-3, Survivin and Cyclooxigenase-2 was measured in a tissue microarray. Cancer-specific and recurrence-free survival after radical cystectomy was recorded. Results: TATI was expressed in 100% of patients without cancer, while 71% of radical cystectomy specimens and 90% of lymph node metastases exhibited decreased or no TATI expression. In radical cystectomy specimens, TATI expression decreased with advancing pathologic stage (P < 0. 001) and lymphovascular invasion (P = 0. 055). In univariate analyses, but not in multivariable Cox proportional hazard regression analyses, decreased TATI expression was associated with increased probability of tumor recurrence and cancer-specific mortality. Decreased TATI expression was correlated with altered expression of Cyclooxigenase-2 (P = 0. 005), p21 (P = 0. 035) and Ki-67 (P = 0. 004). Conclusions: We found that normal urothelium expresses TATI and that TATI expression decreases with advancing tumor stage. While there was no prognostic benefit to TATI when adjusted for standard clinicopathologic features, it seems to play an important biologic role in UCB pathogenesis and invasion. Its association with markers involved in the cell cycle, proliferation and inflammation serves as hypothesis for molecular interactions.

KW - Bladder cancer

KW - Cyclooxygenase-2

KW - Cystectomy

KW - KI67

KW - p21

KW - Recurrence

KW - Survival

KW - TATI

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