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

Epidemiology Bladder cancer is the 11th most common cancer in the world (7th in men, 18th in women) In the United States 17000 deaths occur each year, in Europe there were estimated 52000 deaths in 2012 75% of BC patient present with a disease confined to the mucosa and sub-mucosa

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

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

Urinary Molecular Markers

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

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

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

Materials and Methods 178 patients (118 men and 60 women) average age 57.45 (22-87) years

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

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

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

IV group 13 patients with benign urological disease UBC

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

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

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

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%.

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%.

Summary In monitoring patients who underwent radical cystectomy with an orthotopic intestinal reservoir, the UBC test showed false positive results (mean UBC level was 179.8 ± 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 124.56 ± 0.5 μg/L-the norm to 12 μg/l) in acute urological conditions.

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