THE SIGNIFICANCE OF TUMOR GROWTH MARKERS AND ANGIOGENESIS IN THE DIAGNOSIS OF URINARY BLADDER CANCER

Examinations were made in 121 patients, including 76 patients with urinary bladder cancer (UBC) (superficial (T1N0M) (n = 16) and invasive (T2N0M0 and T3aN0M0) (n = 39) carcinomas, carcinoma invading into and out of the bladder wall (n = 21), including T3bN0M0 (n = 14), T3bN1M0 (n = 6), and with T4N1M1 (n = 1)), 10 patients with cystitis, 10 with urolithiasis, and 25 apparently healthy individuals who made up a control group. The patients with UBC were additionally divided into the following groups according to the degree of tumor cell differentiation: 27 with a low-grade tumor (G1), 24 with a moderate-grade tumor (G2), and 25 with a high-grade tumor (G3). The levels of oncomarkers (urinary bladder carcinoma antigen (UBCA), tissue polypeptide antigen (TPA), tissue-specific polypeptide antigen (TSPA), cytokines (interleukin (IL)-12, tumor necrosis factor-a (TNF-α), and angiogenetic factors (vascular endothelial growth factor (VEGF), transforming growth factor-α (TGFα), fibroblast growth factor (FGF), and insulin-like growth factor-I (IGF-I) were studied by solid-phase enzyme immunoassay. It has been established that measuring the level of cytokeratin oncomarkers (UBC II, TPA, TPS) in the serum, urine, and washings can be, along with cystoscopy, used in the early diagnosis of UBC. A combination of UBC II, TPA, and TPS contents allows speci- fication of the stage of UBC and the grade of tumor cells. The increased levels of TNF-α and IL-12 in patients with UBC confirm the development of a proinflammatory cytokine shift and activation of angiogenesis. The ratio of proangiogenic TNF-α to anti-angiogenic IL12 rises with UBC progression. This may be considered to cause increased vascular permeability and a proneness to bleedings from tumor tissues in patients with UBC. Tumor growth and UBC progression are accompanied by a pronounced increase in the serum levels of growth and angiogenetic factors (VEGF, TGF-α, b-FGF, and IGF-1) as compared to the normal values and to those seen in noncancer diseases. Angiogenetic and growth factors may be used in the early diagnostics of UBC and in the verification of the stage and malignancy of tumor growth.

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