Bykova N. Improvement of differential diagnosis of hyperproliferative processes in the endometrium

A thesis for a candidate degree of medical sciences (doctor of philosophy) in specialty 14.01.01 – obstetrics and gynecology. – Odessa National Medical University, Ministry of Health of Ukraine, Odessa, 2021 The thesis is devoted to the increase of effectiveness of early and differential diagnosis of hyperproliferative processes of the endometrium (HPE) by revealing statistically significant risk factors of the disease, determination of molecular genetic markers of the diagnosis, assessment of the condition of the blood flow in the uterine arteries for the improvement of diagnostic measures of endometrial pathology. It is established that statistically significant risk factors for the development of HPE are age over 50 years, heredity, early menarche, late menopause, infertility, polycystic ovary syndrome, obesity, inflammatory genital diseases, thyroid diseases, diseases of the hepatobiliary system, arterial hypertension, diabetes mellitus. It was found that the diagnostic value of ultrasonography in the diagnosis of HPE increases during Doppler examination of the uterine arteries along with traditional pelvic ultrasound. It was determined that the DNA methylation of SFRP2, GHSR and TNFA genes in HPE is abnormal and changed according to the degree of the pathological changes in HPE in the line: simple non-atypical endometrial hyperplasia – complex non-atypical endometrial hyperplasia – simple atypical endometrial hyperplasia – complex atypical endometrial hyperplasia – endometrial cancer. The operative characteristics of the molecular genetic markers (quantitative content of methylated DNA of the promoter of SFRP2, GHSR and TNFA genes) with the highest sensitivity and specificity in endometrial cancer allow their use in early diagnosis and prediction of endometrial cancer. It has been established that methylation of the first exon of the WIF1 gene is not a pathological mechanism characteristic of HPE, so determining its status in the diagnosis of HPE is not justified. The correlation analysis revealed a strong correlation between the risk factor aged over 50 years and abnormal DNA methylation of SFRP2, GHSR and TNFA genes. Based on the results obtained of the study, an algorithm for early diagnosis and prediction of uterine cancer in women with HPE was elaborated, taking into account statistically significant risk factors, sonographic criteria and molecular genetic markers of the diagnosis.