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Aim to present the results of using single-photon emission computed tomography combined with X-ray computed tomography in the process of diagnosing osteodestructive changes in cancer patients with a rare comorbidity fibrous dysplasia. In the consultative and diagnostic department of the Federal State Budgetary Institution National Medical Research Center of Oncology of the Ministry of Health of Russia, Rostov-on-Don, in 2021, 2 patients with fibrous dysplasia of the skull bones and synchronous oncological diseases were examined. The patients underwent a complex of diagnostic tests: spiral X-ray computed tomography of the head, chest, abdominal cavity and small pelvis, bone scintigraphy, single-photon emission computed tomography combined with X-ray computed tomography of the skeleton bones, and puncture biopsy under ultrasound control. The described clinical observations clearly demonstrate examples of a phased diagnostic oncological search in patients without pathognomonic clinical manifestations and with multiple lesions of the skull bones. An increase in diagnostic information content in the differential diagnosis of fibrous dysplasia of the skeleton bones and bone metastases is facilitated by single-photon emission computed tomography combined with X-ray computed tomography. The combination of these two hybrid technologies provides an opportunity to simultaneous determination of the volume and localization of lesions, timely conduction of differential diagnostics and, in turn, maximum optimization of the examination and management of patients in this category.

e21581 Background: Overexpression of the Bcl-2 protein inhibits apoptosis and promotes carcinogenesis. Stress causes signaling leading to cell buffering with Bcl-2 protein above acceptable levels. The purpose of the study was to analyze the influence of comorbidity – chronic neurogenic pain (CNP) – on the Bcl-2 levels in mitochondria of cells of melanoma, the heart, skin and brain in female mice with growing tumors. Methods: Female С57ВL/6 mice were divided into groups: intact group (n = 21); control group with a CNP model – bilateral sciatic nerve ligation (n = 21); group M – B16/F10 melanoma (n = 63); CNP+M group – B16/F10 melanoma was transplanted 3 weeks after the CNP model creation (n = 63). The concentration of Bcl-2 (ng/mg of protein) was determined in mitochondrial samples by ELISA (Thermo Fisher Scientific, Austria). Statictical analysis of results: Statistica 10.0. Results: CNP decreased the Bcl-2 level in heart mitochondria by 1.3 times (p < 0.05), but increased it in skin and brain mitochondria by 5.8 and 1.3 times, respectively. Similar changes were observed in melanoma growth 1 week after its transplantation: Bcl-2 levels decreased in heart mitochondria by 1.3 times, and increased in the skin and brain by 8.9 and 1.3 times, respectively. After 2 weeks of the tumor growth, Bcl-2 in brain mitochondria decreased by 1.7 times, and it started declining in the skin by the 3rd week – by 4 times, compared to intact females. Bcl-2 in tumor mitochondria exceeded the values in the skin by more than 4 times throughout the experiment. Tumor growth in presence of CNP caused a decrease in Bcl-2 in brain mitochondria by 2.4 times after 3 weeks, and in the heart and skin – by 2 and 1.7 times, respectively, after 2 weeks. Bcl-2 in tumor mitochondria in presence of CNP was lower than in the intact skin on average by 1.8 times throughout the experiment. Conclusions: CNP as a comorbidity caused a modulating effect on the mechanisms of survival and apoptosis of cells both in the tumor and in the main organs providing the vital functions of the body - the brain and heart, and also affects the target organ of melanoma - the skin. The results demonstrated the ability of comorbidity to change levels of Bcl-2 in mitochondria depending on the stage of tumor development.

e22083 Background: The ability of malignant tumors to invasion and metastasis is associated with increased activity of the plasmin/plasminogen family proteases. The purpose of the study was to analyze changes in the plasmin/plasminogen system in tumors and adjacent tissues in patients with cutaneous melanoma in dependence on their gender. Methods: The study included 13 men and 22 women with cutaneous melanoma pT1-2N0M0. Levels of plasmin (PAP), content and activity of uPA, content and activity of tPA, content and activity of PAI were determined by ELISA in homogenates of melanoma (M), perifocal (P) and resection line (RL) tissues after surgical treatment. All patients gave a voluntary informed consent for the study. Skin tissues obtained from 20 non-cancer patients after plastic surgery served as the control. Results: The maximal PAP content in women was found in M – 16.5 times higher than in control, in RL – twice higher; PAP in all tissues of men was on average 7 times higher than in control. The content and activity of uPA and tPA in M were elevated in patients of both genders: in women by more than 3 times, in men by 4.9 and 3.7 times for uPA, respectively, and on average by 1.4 times for tPA. Increased content and activity of PAI-I were observed only in M of women by 74.6 and 2.3 times respectively, while PAI-I levels in men were similar to control values, and its activity was 2.9 times higher. Content and activity of PAI in P and RL tissues of men did not exceed the norm despite an increased activity of uPA and tPA, while in women they were elevated on average by 4 and 1.8 times, respectively. Conclusions: A local increase in the content and activity of the PAI-I plasminogen activator inhibitor in P and RL tissues only in women is a distinctive gender characteristics that can inhibit the spread of melanoma.

e22097 Background: Chronic neurogenic pain (CNP) as a comorbid disease is quite frequent, but its effect on malignant diseases is poorly studied. The risk of cutaneous melanoma in women is higher, but the disease course in men is more severe. The purpose of the study was to reveal the effect of CNP on the levels of sex hormones in the blood of patients with melanoma depending on their gender. Methods: Blood levels of estradiol (E2), estrone (E1), progesterone (P4), testosterone (T) and prolactin (PRL) were measured by ELISA in patients with Т3-4NxM0 melanoma (M): 21 women with CNP (pelvic pain - 7, osteochondrosis – 14), mean age 67.2±2.7 years; 17 men with CNP (osteochondrosis), mean age 65.6±3.1 years. The control group included patients with melanoma similar in age, gender and disease stages without CNP. Results: In women with M+CNP, E2 and P4 were decreased by 1.8 times, while E1 was 1.4 times, T – 2 times, PRL – 1.5 times higher, compared to controls. In men with M+CNP, blood levels of estrogens were unchanged, PRL was 2.5 times lower and P4 and T – 1.3 times higher, compared to the corresponding control levels. Conclusions: CNP upregulated blood levels of androgens in both male and female melanoma patients, and caused the inversion of estrogens only in women with the prevalence of E1 over E2. Gender differences in the CNP influence included the elevation of progesterone and a decrease of prolactin in the blood of men, and P4 deficiency with increased prolactin in women with M+CNP. The specific effect of CNP on the hormonal profile in patients with cutaneous melanoma should be considered in choosing antitumor treatment.

e22084 Background: Gender is an important independent prognostic factor for cutaneous melanoma incidence, and survival in women is better. The purpose of the study was to determine the content of sex steroids and prolactin in tumor, perifocal and resection line tissues in male and female patients with melanoma. Methods: The study included 13 men and 22 women with cutaneous melanoma (M) pT1-2N0M0. Levels of free testosterone (fT), estradiol (E2), estrone (E1), progesterone and prolactin were measured by ELISA in M, perifocal (P) and resection line (RL) tissues after surgical treatment. The average age of patients was in men 54±3.56 years (median age 53, 32-81), in women 65±2.67 years (median age 63, 39-82). Skin tissues obtained from 20 non-cancer patients after plastic surgery served as the control. Results: In M of women, levels of fT, E2 and E1 were elevated on average by 1.3 times, while in men fT was decreased by 1.7 times, and estrogens were increased – E2 by 1.7 and E1 by 3.7 times, compared to the corresponding control levels. In women, fT in P tissues was increased by 1.6 times, while parameters in RL were similar to control values. In men, fT in P and RL tissues was decreased by 3.8 and 2.3 times respectively, and E2 was increased by 1.6 and 1.3 times respectively. E1 in P tissues was decreased by 1.7 times, in RL – similar to control levels. Conclusions: M in patients of both genders has an altered hormonal profile characterized by hyperestrogenia, with the prevalence of E1 and androgen deficiency in men. The expansion of the “tumor field” due to changes in the hormonal profile of P and even RL tissues was established only in male patients with the same morphological prevalence of the process, which may be one of the reasons for the more aggressive tumor course.

e20020 Background: Local imbalance of the main sex hormones can be detected in various malignancies. Recent studies confirm possible intracrine synthesis of steroid hormones by different tissues of the body, including the skin and lungs. The purpose of the study was to reveal changes in steroid balance in lung cancer (LC) patients of both genders. Methods: Estradiol (E2), testosterone (T) and progesterone (P4) were measured in 10% homogenates of tumors, perifocal tissues (p/t) and intact tissues of the lung by radioimmunoassay using Immunotech kits (Czech). The Е2/Т and Е2/Р4 coefficients were calculated. The study included 33 men and 22 women diagnosed with central and peripheral LC (adenocarcinoma, Т2-3N0-1M0), mean age 62±3.4 years, all women were menopausal. The comparison group included non-cancer patients (13 men and 12 women) operated on for chronic inflammatory lung diseases. Results: Levels of E2 and T were increased in all studied samples in patients of both genders with central and peripheral LC, while P4 decreased in men and increased in women. It caused an imbalance of the main steroid groups: the E2T ratio in tumors, p/t and in distant tissues of men with central and peripheral LC on average more than 16 times exceeded that in the comparison group, and E2/P4 by 45, 61 and 38 times, respectively. E2/T in tissues of women with central LC was on average 6 times higher, and Е2/Р4 – 9 times higher than in the comparison group. In women with peripheral LC, steroidal imbalance was detected only in tumor samples, and E2/T and E2/P4 were 14 times higher than in the comparison group; samples of p/t and distant lung tissues did not show statistically significant differences. According to statistical data, peripheral adenocarcinomas are more common in women and are clinically characterized by a less aggressive course, compared to central LC. Conclusions: Patients with lung cancer demonstrated a local steroid imbalance with a marked prevalence of estrogens over androgens and progestins.

e17019 Background: The purpose of the study was to analyze hormonal disorders in tissues of histologically unchanged ovaries of patients with cervical cancer infected with HPV/Chlamydia trachomatis. Methods: We studied levels of estrone (E1), estradiol (E2), free estriol (E3), free (fT) and total (T) testosterone, progesterone (P4), steroid-binding globulin (SBG) and prolactin (PRL) by the ELISA in intact ovaries of 25 patients aged 53.4±3.2 years with cervical cancer T1b-2aN0M0. HPV presence was determined by Е7 protein expression, Chlamydia trachomatis (Ch. tr.) – by IgG and IgА to Ch. tr. and antigen/DNA by ELISA and Real-time PCR. Tissues of intact ovaries obtained during hysterectomy from 22 non-infected women of similar age with endometrial cancer T1N0M0 were used as the control. Results: The data demonstrated a sharp decrease in E2 level by 9.3 times and increase in E1 by 2.3 times in intact ovaries of cervical cancer patients infected with HPV and Ch. tr., compared with the values in controls. Changes were noted in the balance between some estrogen fractions: E1 percentage increased by 5 times, E3 – by 2.4 times and E2 percentage decreased by 4 times. Androgenic status in intact ovaries in cervical cancer was characterized with increased levels of T (by 5.1 times) and fT (by 1.6 times). We noted an increase in SBG concentration by more than 3 times in response to the release of androgens registered in ovarian tissue, as well as significant (by 4.4 times) increase in PRL and decrease in P4 by 1.5 times compared with non-infected tissues. Estrogens to P4 ratio in co-infected patients reduced by 1.6 times, while the PRL to P4 ratio increased by 6.4 times, mainly due to disorders in hormone-producing ovarian function. Conclusions: The development of malignant process in the cervix in a combined HPV and Chlamydia trachomatis infection is accompanied by disorders of the endocrine status in tissues of intact ovaries and shows the undeniable role of consequences of HPV/Chlamydia trachomatis coinfection in this process.

e18081 Background: Ovarian cancer spreads intraperitoneally due to the interaction of tumor cells and the omental mesothelium, creating a metastatic niche and supporting elements of cancer cell expansion such as adhesion, proliferation, migration, and neoangiogenesis. The purpose of the study was to analyze levels of VEGFA, IGF-I, IGF-II and TGFβ1 in omental tissues in ovarian cancer (OC). Methods: The main group included 23 patients with metastatic OC T3-4аN0-3M1; the comparison group – 21 patients with non-metastatic OC T3-4аN0-3M0; the control group – 19 non-cancer patients. Levels of VEGFA, IGF-I, IGF-II and TGFβ1 were measured by standard ELISA methods in tissues of primary tumors and the omentum. Results: Levels of growth factors in the comparison group were not elevated compared to control values. Growth factors in omental tissues in the main group were increased compared to control values: VEGFA – by 2.5 times, IGF-I – by 3.4 times, IGF-II – by 2.5 times, TGFβ1 - by 3.1 times. In the comparison group, the levels in omental tissues were lower than in the main group: VEGFA – by 1.7 times (p < 0.05), IGF-I – by 2.1 times, IGF-II – by 1.6 times (p < 0.05); TGFβ1 did not differ from the levels in the main group. Conclusions: Higher expression of VEGFА in the omentum with metastases can be considered a significant factor in the formation of signaling pathways between metastatic tumor cells and local non-cancer cells. IGF-I and IGF-II trigger the endothelial growth factor. The TGFβ1 activation in the omentum in metastatic ovarian cancer is necessary for the paracrine induction and transition of disseminated tumor and/or stem cells from the "sleeping" to the active state.