1. Role of cytokeratins in the diagnosis and prognosis of the bladder cancer
Giorgi Adeishvili MD
Multiprofile clinic Consilium Medulla

2. Epidemiology
Bladder cancer is the 11th most common cancer in the world (7th in men, 18th in women)
In the United States deaths occur each year, in Europe there were estimated deaths in 2012
75% of BC patient present with a disease confined to the mucosa and sub-mucosa

3. Etiology tobacco smoking
occupational exposure to aromatic amines and hydrocarbons
family history o_O
low fluid intake and ionizing radiation exposure

4. Diagnosis US CT,MRI, IVU Urinary cytology
Urinary molecular marker tests
Cystoscopy

5. Urinary Molecular Markers

6. Aims of study
evaluate diagnostic and prognostic value of cytoceratins UBC and TPA

7. UBC
UBC (Urinary Bladder Cancer) is an immunoassay designed for the determination of soluble cytokeratin 8 and 18 fragments in urine from urothelial tumors.

8. TPA
Tissue polypeptide antigen (TPA) is present in the proteolytic fragments of cytokeratins 8, 18 and 19 as a component of the cytoskeleton of nonsquamous epithelia

9. Materials and Methods 178 patients (118 men and 60 women)
average age (22-87) years

10. I group
46 patient with newly diagnosed BC, confirmed with cystoscopy and histology
UBC

11. II group
108 patients at the stage of follow up of the non- muscle invasive BC
UBC and TPA

12. III group
11 patients after radical cystectomy with orthotropic neo-bladder
UBC

13. IV group
13 patients with benign urological disease
UBC

14. characteristics Sensitivity UBC %
Results I group
characteristics Sensitivity UBC % Т1 89 Т2 91 Т3
100 G1 G3 94
solitary lesion
2 to 7 tumors
<3 cm
>3 cm 90

15. Results II group test result TPA positive 46 10 56 negative 16 36 52
result
Biopsy positive
Biopsy negative
n. of patients
 TPA
positive 46 10 56
negative 16 36 52
 UBC 30 2 32 44 76
Combination
ТРА & UBC 54 12 66 8 34 42
Cystoscopy 62 18 80 28
overal numbers
108

16. Results II group Combination ТРА & UBC TPA 74.2 78.3 82.1 69.2 UBC
Sensitivity %
Specificity  %
PPV
NPV
TPA
74.2
78.3
82.1
69.2
UBC
48.4
95.7
93.8
57.9
Combination ТРА & UBC
87.1
 73.9
81.8
81.0
Cystoscopy
100
60.9
77.5

17. Summary
The use of the UBC test in the diagnosis of primary BC as an additional diagnostic marker is possible, due to the high sensitivity of the method. The UBC test can be considered a reliable prognostic factor for the relapse and progression of the BC, the sensitivity of the test increases in proportion to the activity of the tumor process: the sensitivity for categories T1, T2 and T3 is 89%, 91% and 100%, respectively. Depending on the degree of differentiation of the tumor - G, the sensitivity of the test was 89% for G1, 94% for G3. Depending on the number and diameter of tumors, the sensitivity of the method was N 89%, N 2 93%, D 1 89%, and D 2 90%. The overall sensitivity of the UBC test in patients with a primary bladder tumor was 89%.

18. Summary
Using TPA and UBC tests in monitoring bladder cancer in patients after initial treatment, it was found that the sensitivity of TPA (74.2%) exceeds the sensitivity of UBC (48.4%), but the specificity of UBC (95.7%) is significantly higher, than the specificity of TPA (78.3%). With the combined use of serum and urinary cytokeratins (TPA and UBC), the sensitivity of the method is increased to 87.1%.

19. Summary
In monitoring patients who underwent radical cystectomy with an orthotopic intestinal reservoir, the UBC test showed false positive results (mean UBC level was ± 0.5 μg/L - norm to 12 μg/l) in the absence of recurrence and progression of the disease. The UBC test turned out to be an inaccurate method for the differential diagnosis of RMP with various non- oncological diseases of Urinary System, due to false positive results (the average level of UBC was ± 0.5 μg/L-the norm to 12 μg/l) in acute urological conditions.

20. Thank you for your Attention