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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 most common cancer in European men & 6th leading cause of death

preston-hays
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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 most common cancer in European men & 6th leading cause of death • Cystoscopy & urine cytology: current gold standards for diagnosis & surveillance of BCa • No ideal tumor marker for non-invasive diagnostic & surveillance at the moment

  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 tumor 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 tumor tissue & “normal appearing” bladder mucosa • Post-operative urine sample (1 POD) > for each session of TUR • Controls • 1 urine sample

  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 : 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 in urine of BCa patients & controls • For healthy controls the absent values were substituted by zero Median values presented

  15. Ki67in urine of BCa patients & controls

  16. XIAP in urine of BCa patients & controls

  17. Survivin in urine of BCa patients & controls

  18. Tumor markers vs BCa stage Median values presented

  19. Ki67vs BCa stage

  20. XIAP vs BCa stage

  21. Survivin vs BCa stage

  22. Tumor markers vs BCa grade Median values presented

  23. Ki67 vs BCa grade

  24. XIAP vs BCa grade

  25. Survivin vs BCa grade

  26. Tumor markers at primary & secondary TURBT Median values presented

  27. Ki67 at primary & secondary TURBT

  28. XIAP at primary & secondary TURBT

  29. Survivin at primary & secondary TURBT

  30. Tumor markers for unpaired tissue samples Median values presented

  31. Ki67for unpaired tissue samples

  32. XIAP for unpaired tissue samples

  33. Survivin for unpaired tissue samples

  34. Median of Tu / Median of Tf

  35. Tumor markers for paired tissue samples Median values presented

  36. Ki67 for paired tissue samples

  37. XIAP for paired tissue samples

  38. Survivin for paired tissue samples

  39. Ratio Tu / Tf Median values presented

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