title: A prospective pilot evaluation of urinary and immunohistochemical markers as predictors of clinical stage of urothelial carcinoma of the bladder.
abstract: OBJECTIVE
  To determine, in patients newly diagnosed with bladder cancer, whether p53, epidermal growth factor receptor (EGFR), microvessel density (MVD), urinary bladder tumour antigen (BTA TRAKtrade mark, Bion Diagnostic Sciences, Redmond, WA) and cytology were predictive of clinical stage, evaluated as a function of the clinical stage obtained at transurethral resection of the bladder tumour with and without the addition of clinical grade, a known strong predictor of clinical stage.
  
  
  METHODS
  Between December 1997 and September 1998, 22 men and seven women with a cystoscopic diagnosis of urothelial bladder carcinoma were prospectively enrolled in the study. Urine was collected for cytological and BTA TRAK evaluation before transurethral resection. Tumour grade and clinical stage were obtained from the transurethral resection specimen. MVD was evaluated by computerized calculations of 'optimal MVD' (OMVD) and 'area-weighted MVD' (AWMVD) while p53 and EGFR information was obtained by manual immunohistochemical techniques; 21 patients had sufficient tissue for all immunohistochemical assessments and comprised the study group. Univariate and multivariate comparisons were carried out to determine the contribution of each variable to the prediction of clinical stage.
  
  
  RESULTS
  Although there was a trend, cytological analysis and p53 and MVD immunoreactivity did not significantly correlate with clinical stage, while tumour grade, BTA TRAK and EGFR immunoreactivity did. In a univariate analysis, tumour grade and BTA TRAK were related to clinical stage. In a multivariate analysis, grade was the single best predictor of clinical stage. This analysis also showed that the addition of BTA TRAK and MVD information to grade incrementally improved the predictive ability of grade.
  
  
  CONCLUSIONS
  This pilot study suggests that BTA TRAK and MVD contribute incremental information to tumour grade in predicting the clinical stage of urothelial carcinomas of the bladder; grade remains the most important predictor. These results suggest that further work with BTA TRAK and MVD in more patients and on biopsy material obtained during clinic cystoscopy is warranted for the future development of less invasive methods of identifying patients with invasive bladder cancer.
authors.affiliation: Departments of Urology, Pathology and Molecular Physiology and Biological Physics, University of Virginia Health Sciences Center, Charlottesville, Virginia 22908, USA. theodorescu@virginia.edu
authors.forename: T
authors.initials: T
authors.lastname: Krupski
authors.forename: C
authors.initials: C
authors.lastname: Moskaluk
authors.forename: J C
authors.initials: JC
authors.lastname: Boyd
authors.forename: D
authors.initials: D
authors.lastname: Theodorescu
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D014408:Biomarkers, Tumor / Q000652:urine*; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008833:Microcirculation; D008875:Middle Aged; D009367:Neoplasm Staging / Q000379:methods*; D010865:Pilot Projects; D011379:Prognosis; D011446:Prospective Studies; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D001749:Urinary Bladder Neoplasms / Q000473:pathology* / Q000652:urine
chemical_list: D014408:Biomarkers, Tumor; D016159:Tumor Suppressor Protein p53; D066246:ErbB Receptors