title: Association of tumor-associated trypsin inhibitor (TATI) expression with molecular markers, pathologic features and clinical outcomes of urothelial carcinoma of the urinary bladder.
abstract: OBJECTIVE
  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.
authors: Department of Urology Malmö-Lund, Skåne University Hospital, Lund University, S-20502 Malmö, Sweden. o.patschan@gmx.net
authors: Oliver
authors: O
authors: Patschan
authors: Shahrokh F
authors: SF
authors: Shariat
authors: Daher C
authors: DC
authors: Chade
authors: Pierre I
authors: PI
authors: Karakiewicz
authors: Raheela
authors: R
authors: Ashfaq
authors: Yair
authors: Y
authors: Lotan
authors: Kristina
authors: K
authors: Hotakainen
authors: Ulf-Håkan
authors: UH
authors: Stenman
authors: Anders
authors: A
authors: Bjartell
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D026921:Amino Acid Transport Systems, Neutral / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002295:Carcinoma, Transitional Cell / Q000378:metabolism / Q000473:pathology* / Q000601:surgery*; D049109:Cell Proliferation; D015653:Cystectomy; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008207:Lymphatic Metastasis / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D016016:Proportional Hazards Models; D016896:Treatment Outcome; D001743:Urinary Bladder / Q000378:metabolism / Q000473:pathology; D001749:Urinary Bladder Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000601:surgery*; D019459:Urothelium / Q000378:metabolism / Q000473:pathology
chemical_list: D026921:Amino Acid Transport Systems, Neutral; D014408:Biomarkers, Tumor; C498964:SLC16A10 protein, human