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Introduction

Comparative quantitative evaluation of the XIAP, survivin & Ki67 transcript levels in urine & tissue samples of bladder cancer patients. Introduction. Bladder cancer (BCa)- 5th commonest cancer in European men & 6th leading cause of death

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Introduction

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  1. Comparative quantitative evaluation of the XIAP, survivin & Ki67 transcript levels in urine & tissue samples of bladder cancer patients

  2. Introduction • Bladder cancer (BCa)- 5th commonest cancer in European men & 6th leading cause of death • Cystoscopy & urine cytology - current gold standards for diagnosis & surveillance of BCa • Ideal tumour marker for non-invasive diagnosis & surveillance does not yet exist

  3. Introduction • Survivin - inhibitor of apoptosis protein (IAP) that is selectively over-expressed in most human malignancies • Objectives- • determine suitability of survivin as diagnostic, surveillance (and prognostic) marker of BCa • compare the utility of survivin to other potential tumour markers e.g. Ki67 and XIAP

  4. Materials & Methods • Prospective study • Single, tertiary level referral centre • January - June 2006 • Inclusion criteria- • patients undergoing transurethral resection (TUR) for newly diagnosed BCa, recurrent BCa & cystoscopically suspicious bladder lesions

  5. Materials & Methods • Exclusion criteria- • Patients with PCa, IDC, UTI • Controls • BPH patients • Cystitis patients & • Healthy volunteers

  6. Materials & Methods • BCa patients • Pre-operative urine sample • Intra-operative tumour tissue & “normal appearing” bladder mucosa • Post-operative urine sample (1 POD) • Above repeated for every session of TUR • Control patients • 1 urine sample from each

  7. Materials & Methods • Quantitative evaluation of urinary & tissue levels of survivin, XIAP & Ki67 • Normalized ratios of survivin, XIAP & Ki67 correlated with clinicopathological data

  8. Results • Reference genes used – HPRT & TBP • Negative correlation between reference gene expression & urinary contamination by RBCs & WBCs

  9. Results • BCa patients • 65 recruited • 6 pts with both BCa & Pca, excluded from analysis (59 pts analysed) • Age (median)= 69yrs (34 – 89) • M:F= 39: 20 (66.1% : 33.9%) • Newly dx: BCa recurr= 54: 5 (91.5% : 8.5%) • PSA (median; 36 pts)= 0.90 (0.16 – 12.54)

  10. Results • BCa Stage @ diagnosis (59) • BCa Grade @ diagnosis (59)

  11. Results • cis • Pos: neg= 5: 54 (8.5% : 91.5%) • All with cis harbour high grade (G2/ G3) disease as well • Cytology • Sensitivity= 65.2%; Specificity= 80.0% • PPV= 83.3%; NPV= 60.0%

  12. Results • 59 primary TURBT 42 second op (33 sec TUR, 9 cystec) 8 third op (6 tertiary TUR, 2 cystec)

  13. Results

  14. Tumour markers between BCa & controls Median values presented

  15. Tumour markers for BCa patients Median values presented

  16. Tumour markers vs BCa stage Median values presented

  17. Tumour markers vs BCa grade Median values presented

  18. Tumour markers between first & second TURBT Median values presented

  19. Tumour markers for paired tissue samples Median values presented

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