RADIATION AND CHEMORADIATION THERAPY FOR I STAGE INTERMEDIATE AND HIGH/INTERMEDIATE ENDOMETRIAL CANCER - DESCRIPTIVE ANALYSIS. / PROMENEVA TA KhIMIOPROMENEVA TERAPIIa U LIKUVANNI RAKU ENDOMETRIIa I STADIÏ PROMIZhNOÏ TA VYSOKOÏ GRUP RYZYKU -DESKRYPTYVNYI ANALIZ.

INTRODUCTION: Endometrial cancer ranks the third place in prevalence among all cancers in Ukraine. The surgicaltreatment and subsequent adjuvant treatment is planned according to the patient's risk group. The choice of radi-ation therapy and the need to add chemotherapy determines the level of recurrence-free survival. OBJECTIVE: The aim of the study was to analyze the database of treated patients in National Cancer Institute, with Istage endometrial cancer intermediate and high-intermediate group; determination of the most frequent choice ofradiation treatment in accordance with the risk group of patients with a hysterectomy with salpingo-oophorectomyfor further observation and evaluation of diseasefree survival. MATERIALS AND METHODS: Retrospective was analysed 245 patients with high and intermediate risk groups with stageI endometrial cancer. The exclusion criteria were: low-risk patients, stages II-IV and non-endometrioid histologi-cal variant. RESULTS: According to the analysis, there were 122/245 (49.8 %) patients of high risk group, 123/245 (50.2 %) ofintermediate risk group. High-risk patients underwent external beam therapy and brychytherapy, supplemented bychemotherapy in 5.8 % of cases (7 patients), brachytherapy with external beam therapy was performed in 58.2 % ofcases (71 patients), brachytherapy - in 8.1 % of cases (10 patients), external beam therapy was performed in 27.9 %cases. Intermediate and high-intermediate risk patients were distributed as follows: brachytherapy was performedin 41.5 % of cases (51 patients), brachytherapy with external beam therapy - 54.5 % (67 patients), external beamtherapy was performed in 5 patients. CONCLUSION: Brachytherapy is available for patients with intermediate risk endometrial cancer and external beamtherapy with possible addition of brachytherapy is recommended for high-intermediate and high-risk groups, espe-cially in patients with lymphatic vascular involvement. All patients are monitored for further assessment of recur-rence-free survival.

Features of recurrence of endometrioid type endometrial cancer of I stage.

The aim of this study was to determine the rates of recurrences of stage I endometrial cancer (EC) and features of their localization depending on the clinical and pathological characteristics of the tumor and methods of patients' treatment. PATIENTS AND METHODS: The study included 968 patients with stage I endometrioid EC, who underwent surgical treatment in the Department of Oncogynecology of the National Cancer Institute in 2015-2019. Surveillance of patients lasted from January 2015 to December 2020, with a minimum follow-up period of 1 year from the date of surgery. Adjuvant radiation or chemotherapy was performed depending on the clinical and pathological characteristics of the EC case. RESULTS: During the follow-up period, recurrences were observed in 7.0% of cases and were most often found in stage IC of low differentiation grade. It was found that during surgical treatment without adjuvant therapy relapses occurred in 12-36 months after the start of treatment, with adjuvant radiation therapy - in 6-18 months, and with adjuvant chemotherapy - in 32-60 months. Recurrences most often occurred in patients with EC who underwent surgical treatment in combination with chemotherapy (p < 0.05). The lowest number of recurrences was recorded among patients who underwent surgery as an only treatment. The best 5-year survival rate was observed in the group of patients with surgical treatment (93%), and the worst - in the patients treated with combination of surgery and chemotherapy (57%). In patients without recurrences, the survival rate after treatment was 97%, while in patients diagnosed with relapses, the survival rate was 65%. CONCLUSION: Despite the predominantly favorable course of EC stage I, some patients develop relapses. The rate and localization of recurrences depend on the histological structure of the tumor and treatment regimens of the EC patients.

Expression of microRNA in tumor cells of endmetrioid carcinoma of endometrium.

BACKGROUND: It is known that more than half of the genes encoding human proteins are regulated by various microRNAs (miRNAs, miR), the expression of which may be associated with various pathological conditions. At the same time, the question of assessing the relationship between the expression of particular miRNAs and the aggressive molecular subtype of endometrial cancer remains open. Aim of the study was to determine the relationship between the expression of miR-34a, miR-125b, miR-142 and miR-101 in endometrioid carcinomas of the endometrium (ECE) and the features of the disease course. MATERIALS AND METHODS: The samples of surgical material of 51 patients with ECE (mean age 59.8 ± 7.1 years), I-III stage were investigated using morphological, immunohistochemical methods, real time polymerase chain reaction (PCR), cytofluorometry. RESULTS: In endometrial tumors with high proliferation index (< Me), the expression of miR-34a, miR-142 and miR-125b significantly decreased (1.8, 2.7 and 1.5 times, respectively) compared with those in ECE with low proliferation index (> Me). The expression of all studied miRNAs was lower in G3 tumors and those that deeply invaded the myometrium compared to G2 carcinomas and tumors with an invasion of > 1/2 myometrium and significantly decreased in tumors of patients with low stage III compared with stage I-II. The high (< Me) microvessel density in ECE was associated with a significant decrease of miR-125b and miR-101 expression, and the presence of signs of epithelial-mesenchymal transition - with a decreased expression of miR-34a and miR-101. CONCLUSIONS: The study revealed a significant heterogeneity of expression of miR-34a, miR-125b, miR-142 and miR-101 in ECE, which is associated with changes in morphofunctional characteristics of endometrial carcinoma.

DNA damage in tumor cells and peripheral blood lymphocytes of endometrial cancer patients assessed by the comet assay.

To date, genome instability is considered to be a common feature not only of tumor cells, but also of non-malignant cells of cancer patients, including peripheral blood lymphocytes (PBLs). The issue of the association between genome instability in tumor cells and PBLs, as well as of its relationship with tumor progression remains poorly understood. AIM: To evaluate the level DNA damage in tumor cells and PBLs of endometrial cancer (EC) patients with regard to clinical and morphological characteristics of the patients. MATERIALS AND METHODS: DNA damage was assessed in 106 PBLs samples and 42 samples of tumor cell suspension from EC patients by comet assay. PBLs from 30 healthy women were used as control. The level of DNA damage was expressed as the percentage of DNA in the comet tails (% tail DNA). RESULTS: It was revealed that the amount of DNA damage in PBLs of EC patients was 2.2 times higher in comparison with that of healthy donors (8.3 ± 0.7 and 3.7 ± 0.4% tail DNA, respectively) (p < 0.05). In this study, no association between the levels of DNA damage in endometrial tumor cells and PBLs was observed (r = 0.11; p > 0.05). The amounts of DNA damage both in tumor cells and PBLs were not related to the degree of tumor differentiation as well as the depth of myometrial invasion, but depended on the body mass index (BMI) of EC patients: high level of lesions was observed in patients with elevated BMI values. Furthermore, the level of DNA damage in tumor cells was associated to familial aggregation of cancer and was significantly higher in endometrial cells from patients with family history of cancer vs that from EC patients with sporadic tumors (32.3 ± 2.9 and 22.8 ± 1.8% tail DNA, respectively) (p < 0.05). It was also found that for women who had high level of DNA damage in PBLs, the risk of EC was greater (odds ratio value of 3.5) compared to those with low level of such lesions. CONCLUSION: Genome instability that appears as an increased level of DNA damage in tumor cells and PBLs of EC patients is associated with BMI and family history of cancer and can reflect a predisposition to cancer.

The study of mismatch repair in endometrial cancer patients with a family history of cancer.

AIM: To assess the expression of mismatch repair (MMR) proteins MSH2 and MLH1 and carry out microsatellite analysis in patients with endometrial cancer (EC) with regard to the family history of cancer. MATERIALS AND METHODS: Morphological and immunohistochemical study was performed on tumor tissue samples of 49 EC patients. Microsatellite instability was determined using PCR with primers which flank microsatellite region BAT-26. RESULTS: A tendency to a decreased expression of both MSH2 and MLH1 markers in a group of EC patients with a family history of cancer as compared with a group without aggregation of cancer in family history was observed (labeling index - LI - was 36.1 ± 8.1% and LI 20.7 ± 9.1% versus LI 48.0 ± 5.8% and 33.8 ± 5.8%, respectively). It was determined that the number of EC patients with tumors deficient by expression of MMR markers was reliably higher in a group of patients with a family history of cancer than in a group of patients without aggregation of cancer in family history (р < 0.05). It was shown that in a group of EC patients with a family history of cancer, MMR-proficient tumors were detected in 38.5% of cases. Microsatellite instability was determined in 10.7% of EC patients including one patient with aggregation of Lynch-associated tumors in family history. CONCLUSION: Family history of cancer of EC patients is associated with malfunctioning of the MMR system as well as may be related to alternative molecular mechanisms.

The study of chromosomal instability in patients with endometrial cancer.

AIM: Study is devoted to evaluation of sensitivity of peripheral blood T-lymphocytes (PBL) of patients with endometrial cancer (EC) to genotoxic effect of bleomycin and detection of patients with hidden chromosomal instability. METHODS: PBL of 24 EC patients (mean age 58.9 ± 2.9) and 10 healthy women-volunteers (mean age 55.7 ± 2.3) were subjected to cytogenetic analysis. RESULTS: Mean spontaneous level of chromosomal aberrations (CA) per 100 analyzed lymphocytes (CA/100) of healthy women has equaled 2.7 ± 0.6, i.e. has not exceeded maximal values of healthy population and was significantly lower (p < 0.05), than in PBL of EC patients (6.9 ± 0.6). After incubation of PBL with bleomycin, number of CA/100 significantly was increased both in control (11.5 ± 1.3) and in EC patients (21.9 ± 1.0). Spontaneous chromosomal instability has been observed in 41.7%, increased sensitivity to bleomycin - in 54.2% and hidden chromosomal instability in 37.5% of patients with EC. It has been shown that level of specific damage of genome in EC patients has constituted 2·10(-5), and after exposure with bleomycin, it was increased 4.5 times (9·10(-5)) that was significantly higher (p < 0.05) compared to control (8·10(-6) and 1.0·10(-5), respectively). CONCLUSION: These results have demonstrated that PBL of most patients with EC are characterized by apparent genome alterations, which are manifested by increased number of spontaneous and induced chromosomal damages, hypersensitivity to mutagens and hidden chromosomal instability.

Clinical significance of hormonal receptor status of malignant ovarian tumors.

OBJECTIVES: To study hormonal receptor status (HRS) of malignant ovarian tumors (MOT) and determine its clinical significance. PATIENTS AND METHODS: Retrospective analysis of case histories of 284 patients with MOT of different genesis of I-IV stages was carried out; immunohistochemical study of paraffin-embedded tissues. The HRS for serous, mucinous ovarian cancer (OC) and sex cord-stromal tumors (SCST) was studied. The phenotype of tumors by HRS in patients with serous OC was determined; overall and relapse-free survival in these patients was evaluated depending on the tumor HRS. RESULTS: Positive expression of ER has been registered in 66.4% of patients with serous OC, PR - in 63.4%, TR - in 53.0%; in patients with mucinous OC - 88.0; 84.0; 60.0%, respectively. Positive staining of cells of stroma-cellular tumors has been observed in 74.1% of patients for ER and 77.8% - for PR and TR. The highest number of patients with tumor phenotype ER+PR+TR+ has been observed in postmenopause - 52.4%, especially in late postmenopausal period - 39.0%. The lowest percentage of patients with mentioned phenotype has been marked in reproductive age - 20.7%. Most patients of reproductive period had phenotype of tumor ER-PR-TR- (35.1%), in late postmenopause this phenotype has been observed only in 16.2%. The patients with serous OC with the positive tumor HRS demonstrated the low indices of overall and relapse-free survival compared to the patients with receptor-negative tumors concerning all steroid hormones (р < 0.05). CONCLUSIONS: Positive HRS was registered in serous, mucinous OC and in SCST, high percentage of tumors with expression of all receptors of steroid hormones was observed at that. The highest frequency of tumors with positive HRS was recorded in patients with serous OC of late postmenopausal period. The patients with serous OC with receptor-positive tumor phenotype showed the rates of overall and relapse-free survival significantly lower compared to the patients with receptor-negative phenotype of OC. Positive HRS, the same as strong expression of TR in patients with serous OC, is a predictive factor of unfavorable course of tumor process. HRS of MOT can be regarded as the additional criterion for solution of a question concerning application of hormonal therapy as a component of complex treatment for the patients.