THE IMPORTANCE OF ANGIOGENESIS IN THE FORECAST OF RECURRENCE AND PROGRESSION OF A NON-INVASIVE UROTELIAL BLADDER CANCER

The aim of the work was to study angiogenesis in non-invasive urothelial cancers of the bladder (NUCB) to identify the criteria for recurrence and progression of the disease. Materials and methods. The material, urothelial cancers of the bladder stage T1, without invasion into the muscular layer of the wall of the organ, was obtained in the Kharkiv Regional Clinical Center of Urology and Nephrology named after V.I. Shapovalov. The number is 42 cases. The average age of patients was 66.4 ± 7.2 years; men were 83.3% (35/42), women –16.7% (7/42). The material was divided into groups: NUCB without recurrence - group I (14 cases), NUCB with recurrence without progression - group II (14 cases) and NUCB with recurrence and progression in the form of invasion into the muscular layer of the wall - group III (14 cases). In order to exclude the effect on the study results of tumor differentiation factor, in each of the study groups an equal number of cases of high and low grade NUCB were taken: eight low grade NUR NUCB and six cases of high grade NUCB. Cancer differentiation was taken into account according to the latest WHO classification, 2016. Results and discussion. Microvessel density (MVD) in NUCB was 32,71±4,22 and ranged from 12.8 to 44.6. MVD in the stroma of NUCB increased with an increase in the degree of tumor malignancy, but the level of vascularization did not directly affect the prognosis of the disease - differences between groups of studies in terms of MVD are not significant (p>0.05). A positive correlation was found between the level expression of VEGF and MVD (r = 0.677, p<0.05). So weak expression of VEGF was observed in 28.6% (12/42) cases, while the average MVD was 21.7 ± 6.0; moderate expression of VEGF was observed in 71.4% (30/42), the average MVD value was 37.0 ± 8.25 (p<0.001). The VEGF expression in high grade NUCB was more intense than in low grade NUCB. So a low level of VEGF reaction (up to 10% of tumor cells) was observed in 41.7% (10/24) of the low grade NUCB and only in 11.1% (2/18) of the high grade NUCB (χ2 = 4.7 p<0,03). Accordingly, a moderate level of VEGF expression (with a reaction in 11–50% of tumor cells) among low grade NUCB was 58.3% (14/24), among high grade NUCB it was 88.9% (16/18) (p<0 ,03). The found relationship between NUCB differentiation and neoangiogenesis indicators - expression of VEGF in tumor cells and MVD of the stroma, as well as correlation between these marks - indicate the role of tumor cells in neoangiogenesis through VEGF expression of them and increasing neoangiogenesis as tumor differentiation decreases. Considering the expression of VEGF in NUCB, depending on their belongings to the study groups, approximately the same reaction level was detected: the average expression of VEGF in group I was 1.71 ± 0.46, in group II - 1.64 ± 0.49, in III group - 1.78 ± 0.42, which indicates a limited value of VEGF for the prediction of recurrence and progression of the disease. Conclusions. The role of VEGF in neoangiogenesis of NUCB was confirmed, which is determined by the direct correlation between the expression level of VEGF and DMV (r = 0.677, p <0.05). As the NUCB differentiation decreases, an increase in tumor vascularization is observed (p <0.01), which is caused by an increase in VEGF expression by tumor cells (p<0.03). The studied indices of neoangiogenesis - DMV and VEGF - are of limited importance for the prediction of recurrence and progression of NUCB.