The relevance of studying endometrial hyperplastic processes (EHP) is determined by the significant prevalence of this pathology among women of various ages, its high potential for progression to endometrial cancer, and its impact on reproductive function, specifically as a cause of infertility. EHP is one of the most common gynecological diseases worldwide. There are no statistical data on its prevalence in Ukraine. Improving diagnosis and treatment will contribute to better overall health and quality of life for patients.
EHP includes endometrial hyperplasia (EH) and endometrial polyps (EP), among which glandular, glandular-fibrous, and fibrous EP (GEP, GFEP, and FEP, respectively) are distinguished. EHP is an estrogen-dependent hyperproliferative pathology of the uterus, occurring against the background of chronic hyperestrogenism. Estrogens exert their effects through estrogen receptor alpha (ERα), which is encoded by the ESR1 gene. Modifications in the ESR1 gene lead to disruptions in hormone receptor receptivity. The PvuII single nucleotide polymorphism (SNP) (rs2234693) occurs due to the substitution of thymine (T) with cytosine (C) in the first intron of the gene. Cyclooxygenase-2 (COX-2) plays a role in regulating resistance to apoptosis, inducing proliferation, and angiogenesis. It serves as an indicator of the neoplastic transformation of normal cells into tumor cells.
Given the relevance of this topic, the presented dissertation is devoted to studying the prevalence of endometrial hyperplastic processes in the Sumy region, the features of their clinical manifestations, and their morphological, immunohistochemical, and molecular-genetic diagnosis.
To achieve the set goal, a cohort of 95 patients with a diagnosis of EH or EP, histologically verified after surgical treatment at the Sumy Regional Clinical Oncology Center (Sumy, Ukraine) from 2020 to 2022, was collected. These patients comprised the main group. For studying the PvuII polymorphism of the ESR1 gene, an additional control group was formed, consisting of 80 women without EHP.
Data collection and analysis of the number of treated EHP cases in the Sumy region from 2011 to 2020 were carried out. The scientific research results indicated an increase in the overall incidence of EHP, with the peak incidence occurring in 2016. A correlation between the incidence of EHP and age was observed. In older age groups, a predominance of localized forms of EHP with a fibrous component was found.
The number of asymptomatic cases of EHP is increasing. In 51% of cases, they were associated with a higher body mass index or obesity. Approximately one-third of EHP cases are characterized by a recurrent course, the presence of concomitant hyperproliferative diseases (endometriosis, uterine leiomyoma), as well as extragenital pathology, emphasizing the need for a comprehensive approach to diagnosing and treating these patients.
Analysis of the morphological characteristics of EHP showed a predominant increase in the gland-to-stroma ratio of the endometrium compared to normal proliferative endometrium. In EH, numerous irregularly arranged glands of various shapes and sizes, sometimes cystically dilated, were observed. EPs formed from the basal layer of the endometrium and were characterized by localized overgrowth of glands and stroma. GFEP was characterized by a pronounced stromal fibrosis.
The study examined the features of ERα and COX-2 expression in EHP. Positive ERα expression was found in all studied samples, both in the epithelial and stromal components, with a patchy pattern. COX-2 expression was detected in the epithelium of all tissue samples with EHP, with the highest level of expression observed in the GFEP group.
Immunohistochemical diagnosis of ERα and COX-2 expression in EHP is an important tool for a detailed assessment of pathological changes in the endometrium, allowing for differential diagnosis between different types of this pathology, determining the risk of recurrence, progression, and malignant transformation, especially in women with risk factors and a burdensome family history.
For the first time, the distribution of genotype variants for the PvuII polymorphism of the ESR1 gene in women with EHP in the Sumy region was studied. The relationship between the PvuII polymorphism and the histological type of EHP, patients' anthropometric characteristics, age categories, anamnesis data, as well as concomitant genital and extragenital pathologies was investigated. The relationship between ERα and COX-2 expression levels depending on genotype according to the PvuII polymorphism of the ESR1 gene in EHP was studied.
The scientifically proven results deepen the understanding of the molecular basis of the pathogenesis of EHP. These data highlight the need to explore other genetic or non-genetic factors that may influence the development of EHP.
