Introduction

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 • Controls • 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. 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. BCa patients Stage @ diagnosis (59) • No tumour (11) 18.6% • Superficial (38) = Ta+T1 64.5% • Invasive (10) = T2 16.9% Grade @ diagnosis (59) • No tumour (11) 18.6% • Low (14) = G1 23.8% • High (34) = G2+G3 57.6%

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

13. Controls

14. Tumor markers between BCa patients & controls Median values presented

15. Ki67

16. XIAP

17. Survivin

18. Tumor markers vs BCa stage Median values presented

19. Ki67

20. XIAP

21. Survivin

22. Tumor markers vs BCa grade Median values presented

23. Ki67

24. XIAP

25. Survivin

26. Tumor markers between first & second TURBT Median values presented

27. Ki67

28. XIAP

29. Survivin

30. Tumor markers for unpaired tissue samples Median values presented

31. Ki67

32. XIAP

33. Survivin

34. Tumor markers for paired tissue samples Median values presented

35. Ki67

36. XIAP

37. Survivin

38. Ratio Tu / Tf