F.I. Kostyev, L.I. Krasilyuk, R.V. Bakhchiev, D.A. Kuznietsov, A.V. Rudenko

PIN - precancerous prostatic disease, pathogenetic substantiation of patients monitoring

A large attention is given to the study of certain features of the precancerous and early stages of carcinogenesis in prostate cancer. The proliferative inflammatory atrophy (PIA) and prostatic intraepithelial neoplasia (PIN) are considered as preneoplastic process characterized by pathological changes in the epithelium of prostate gland.

The success and effectiveness of the treatment are depended on the on the timely performed complex of diagnostic procedures. The early diagnosis and timely treatment are the most effective way to reduce the morbidity and mortality from prostate cancer. The experimental model was built on 159 male Wistar rats with age 3 mounth, weight 150± 20 g, which were kept in standard laboratory biological clinics Odessa National Medical University.

Experimental PIN model is original, developed by us and protected by a patent for an invention (pat. № 20 of 27/10/2008) and performed by subcutaneous injection of sinestrol and testosterone propionate hormones. Sinestrol had injected by 40 mg/kg per week for 1,2,3 and 6 months from the start of the experiment. Testosterone propionate had administered by 150 mg/kg for 4,5,7 and 8th months.

The concentration of lipid peroxidation products (malonic dialdehyde, diene conjugates), the activity of antioxidant enzymes (superoxide dismutase, catalase) in the blood and tissues of the prostate were studied in groups of animals. The phytoestrogen - EKSO in dose 0.2 mg/kg daily for 8 months was injected intramuscularly to a group of animals to identify opportunities for prevention in the event PIN. The role of genetic monitoring of PIN differentiation in benign prostatic hyperplasia detected by analyzing methylation levels of promoter region of gene APC, GSTP1, RARІ, that made it possible to assess the role of PIN as precancer of prostate and guide the method of patients observation.

The results of morphological changes had four main periods of structural changes. There was a gradual icrease of lipid peroxidation, the shift in the balance of lipid peroxidation - antioxidant protection violations that increase the reduction level of antioxidant enzymes. The subsequent injection of hormones for creation of PIN from a low to a high degree intensified such dependence on macro organic level.

The morphological studies of the ECSO effect performed as a preventive action of the PIN formation and protection influence on the course with already formed the PIN for further justification and for pathogenetic treatment of precancerous PIN as prostate cancer that was modeled in the experiment. Thus the using of ECSO promoted the reduction the DC content in the tissue of the prostate gland and blood serum to 98.5%; 97.4% The MDA was significant statically decreased to 32.2% and 21.5% that was equal against to the control with 102.3%; 105.8%.

Thus given facts demonstrate that the phytoestrogen EСSO reduces greatly the formation of PIN within 4 months of the administration. Meanwhile its prolonged using is capable to inhibit the development of involutional changes in the body, particularly in the prostate gland. The ECSO using with such moderated injection of sinestrol and testosterone propionate was prevented to development experimental PIN. The molecular genetics properties such as precancerous PIN were studied in 76 patients with BPH.

The methylation promoter area of tumor growth suppressor gene GSTP1, APC and RARІ, was the subjects of study. Thus BPH samples containing PIN and atypical proliferation differs with higher level of methylation compared with samples of BPH without them.