Histopathological evaluation of endometrial tissue in patients of abnormal uterine bleeding

Background: Abnormal uterine bleeding (AUB) is one of the commonest complaints in the gynecology OPD. It is also one of the most common reason for hysterectomy among Mizo women. Endometrial biopsy is a gold standard and first step for diagnosis of AUB in a low resource setting like the North-east states of India. The aim of the study was to evaluate the histopathology of endometrium for proper management of AUB cases.Methods: This was a prospective study done to evaluate the histopathology of all the cases of AUB who attended gynaecology OPD, from the year 2018 to 2020. This study comprised of 668 AUB cases and material of the study was endometrial tissue of the cases of Abnormal uterine bleeding collected by dilatation and curettage, and sent for histopathological study to the department of pathology.Results: Most of the abnormal uterine bleeding patients was in the age group of 40 to 49 years, and the most common histopathological finding was proliferative endometrium, 35.5% followed by disordered proliferation, 21%. 14 cases of carcinoma endometrium were found among the age group above 40 years.Conclusions: The research evident that all the women above 40 years old need to undergo screening, keeping in mind the higher risk of carcinoma in the older age group of women.

Local cytokine production in patients with external genital endometriosis

The article presents the results of the investigation of cytokine production by endometrioid heterotopias in organotypic cultivation in comparison with the cell secretory activity of peritoneal fluid and endometrial tissue in women with external genital endometriosis. The obtained results show systemic changes of regulation of cytokine production in the process of external genital endometriosis development.

Unique Sensitivity of Uterine Tissue and the Immune System for Endometriotic Lesion Formation

Endometriosis is a debilitating disease that affects about 10% of reproductive-aged adolescents and women. The etiology of the disease is unknown; however, a prevailing hypothesis is that endometriosis develops from retrograde menstruation, where endometrial tissue and fluids flow back through the oviducts into the peritoneal cavity. There is no cure for endometriosis, and symptoms are treated palliatively. Despite the advances in knowledge, the complexity of endometriosis etiology is still unknown. Recent work by our group suggests that the initiation of endometriosis is immune-dependent. Using a mouse model of endometriosis, we hypothesized the initiation of endometriosis is immune regulated and uterine endometrium specific. In the absence of a functional immune system non-obese diabetic/severe combined immunodeficiency (NOD/SCID mice), endometriotic lesions did not form. Uterine endometrial tissue forms endometriotic lesions, whereas tissues with differing basal expression levels of estrogen receptor alpha (ESR1) and estrogen receptor beta (ESR2), similar cellular composition to uterus (i.e. bladder, mammary gland, and lung), and treated with estradiol did not form lesions. As MMP7 is known to play a major role in the organization/reorganization of the endometrium during the menstrual cycle, blocking metalloproteinase (MMP) activity significantly decreased the invasive properties of these cells. Together, these findings suggest that endometriosis is immune and uterine specific and that MMP7 likely plays a role in the ability of uterine tissue and the innate immune system to establish and maintain endometriotic lesions.

Endometrial Cytokines in Women with Reproductive Disorders

The purpose of this research was to study changes in endometrial cytokine concentrations in women suffering from reproductive disorders with and without chronic endometritis (CE) to justify pathogenetic treatment. Methods and Results: The study included 100 women of reproductive age with reproductive disorders. Group 1 included 50 patients with reproductive disorders and CE; Group 2 included 50 patients with reproductive disorders and without CE. Later on, all patients were divided into the following subgroups: Sub1A (n=31), and Sub2A (n=16) with an isolated bacterial flora, Sub1B (n=19) and Sub2B (n=34) with the absence of bacterial flora. The control group consisted of 31 fertile women. Endometrial aspiration pipe biopsy was performed on days 4-9 of the menstrual cycle (middle proliferative phase) using a disposable intrauterine probe (Taizhou Kechuang Medical Apparatus Co., Ltd, China) followed by histological examination of endometrial tissue. Laboratory diagnostics for sexually transmitted infections (STIs) was performed using the bacterial culture method. For the diagnosis of viral infection (HPV, HSV, CMV), cervical samples were studied using PCR. If STIs were detected, the patients were excluded from further research. Ultrasound examination of the pelvic organs was performed using the Aloka-5500 device with a 7MHz vaginal probe in two-dimensional visualization mode. The concentration of cytokines (IL-1β, INF-γ, TNF-α, ILs-4,6,8,10) in the endometrium was determined using the Protein Contour test systems (Saint Petersburg) and Multiskan EX ELISA Analyzer (Germany). In both groups, reproductive disorders were accompanied by hypoprogesteronemia and relative hyperestrogenemia, significantly apparent in CE. We found a 3-fold increase in the level of tissue pro- and anti-inflammatory cytokines (IL-1β, IL-4,6,10, INF-γ), and a 4-fold increase in the level of TNF-α and IL-8 in Group 1, compared to the CG. In Group 2, we found a 1.4-fold increase in the levels of IL-1β and INF-γ, compared to the CG. In Sub 1a, the levels of IL-6 and IL-8 were significantly higher than in the control group. In Sub1A, the isolated bacterial flora caused a cytokine inflammatory response characterized by a significant increase in the concentration of INF-γ and TNF-α, compared to Sub2A and Sub2B (P<0.05). In Sub1A, we found a tendency towards a decrease in the tissue levels of IL-4 compared to Sub1B and Sub2B; the IL-10 level was significantly lower than in Sub2B (P=0.0009) Conclusion: The results obtained in the present study showed the peculiarities of changes in cytokines at the level of endometrial tissue both in chronic inflammation of the endometrium and in its absence in women with reproductive disorders. The severity of the immune response is significantly higher in patients with CE, with the most significant change in the role of IL-10.

Immunohistochemical Analysis of the Expression of the Glycodelin Cytokine in Endometrial Tissue and the Endometrial Polyp, Before and After Hysteroscopy, in Infertile Female Patients

An endometrial polyp is most commonly a benign, localized proliferation of the glands and the endometrial stroma, covered with epithelium and protruding above the level of the mucosa. These polyps are most often diagnosed during investigation into the causes of irregular menstrual bleeding or infertility. It is produced in the highest concentration during the secretory phase of the endometrial cycle. The level of glycodelin reaches its peak 12 days after ovulation. The aim of this paper was to determine the changes in the immunohistochemical expression of glycodelin at the level of the endometrium and in the tissue of the polyp, before and after hysteroscopic polypectomy, in infertile female patients with an endometrial polyp, and in the endometrial tissue of female patients without an endometrial polyp. The study included 82 infertile female patients. The infertile patients were divided into two groups. The first was the experimental group which included 56 infertile female patients who had an endometrial polyp. The second group was the control group, composed of 26 infertile female patients who did not have an endometrial polyp. The results obtained primarily indicate the existence of changes in the immunohistochemical expression of the cytokine glycodelin in the female patients from both the experimental and the control group, not only prior to but also after hysteroscopy. A larger number of patients who have an endometrial polyp show a lack of glycodelin expression, more pronouncedly so in the bioptate of the endometrium than in the endometrial polyp.

PROSPECTIVE STUDY OF THE EFFECTIVENESS OF DIFFERENTIATED THERAPY OF ENDOMETRIUM HYPERPLASIA WITHOUT ATYPIA IN WOMEN IN REPRODUCTIVE AGE

The paper considers the issues of improving the effectiveness of treatment of endometrial hyperplasia without atypia in women of reproductive age with the use of progestins as a pathogenetic therapy and should be personalized (targeted) taking into account the receptor sensitivity of endometrial tissue to progestins. The positive effects of progestin use are mainly due to the expression of progesterone receptors in the endometrial tissue, which must be taken into account during hormone therapy. A prospective study was performed in 60 patients of reproductive age with abnormal uterine bleeding, who according to the results of histological examination of endometrial tissue was diagnosed with endometrial hyperplasia without atypia. All patients were treated with micronized progesterone at a dose of 400 mg / day continuously for 6 months. To determine the effect of the use of progestins was performed by studying the expression of receptors for estrogen (ER) and progesterone (PR) in histological blocks of the endometrium by immunohistochemistry. In all women there was a significant expression of EP in endometrial cells, which led to its proliferative activity against the background of reduced expression of progesterone receptors by 65%, which caused no effect of therapy in 25% of women. Studies have shown that when deciding on the appointment of micronized progesterone for the treatment of endometrial hyperplasia without atypia, it is recommended to study the expression of progesterone receptors in endometrial tissue to clarify the possibility of a pharmacological effect. Treatment of endometrial hyperplasia without atypia with progesterone drugs is not effective in low expression of progesterone receptors in endometrial tissue. Based on this, we can identify a group of women with progesterone-resistant hyperplasia who require other treatments.

Expression of Cell Adhesion Molecules in Endometrial Tissue and Endometrioid Adenocarcinomas

Endometrioid endometrial adenocarcinomas are the most common histological variant of malignant tumors in the uterine cavity. In turn, the features of expression by neoplastic cells of intercellular adhesion molecules are a reliable prognostic factor in the progression of malignant tumors. One of the important indicators of cancer progression is E-cadherin, which determines the strength of intercellular adhesion and the ability of cells to spread. Among other adhesion molecules, considerable attention has recently been paid to the molecules of cell adhesion of carcino-embryonic antigen 1 (MCA-REA1). Therefore, the purpose of the study was to study the expression of E-cadherin and MCA-REA1 in normal endometrium and endometrioid adenocarcinomas. Materials and methods. To achieve this purpose, we performed tissue studies of 10 samples of normal endometrium and 30 samples of endometrioid endometrial adenocarcinoma (8380/3). Morphological features of neoplastic tissue were studied by hematoxylin and eosin staining. Visualization of E-cadherin and MCA-REA1 receptors was determined using the appropriate antibodies and the UltraVision Quanto Detection System HRP DAB Chromogen (Thermo scientific, USA) in similar areas of the tumor on serial sections. Results and discussion. It has been shown that endometrial tissue demonstrates different expression of MCA-REA1 and E-cadherin receptors in the normal state and in endometrioid adenocarcinomas. This indicates the absence of any functional correlation between them. Expression of MCA-REA1 was detected on the apical surface of the luminal and glandular columnar epithelium. In contrast, the endometrioid endometrial carcinoma tissues showed the pronounced heterogeneous location of MCA-REA1 in tumor cells. Moreover, due to the tumor dedifferentiation, these proteins disappear from the cell surface. On the other hand, E-cadherin is normally localized in intercellular contacts and epithelial-mesenchymal junctions. During carcinoma dedifferentiation, the intensity of E-cadherin expression decreased, which was accompanied by an increase in nuclear polymorphism of cancer cells and focal separation of cells from the total tumor mass. Conclusion. The variability of the expression patterns of MCA-REA1 and E-cadherin in the dedifferentiation of endometrioid adenocarcinoma may be an indicator of neoplastic transformation and progression of the malignant process

Menstruation Dysregulation and Endometriosis Development

Endometriosis is a common gynecological condition characterized by the growth of endometrial-like tissue outside of the uterus which may cause symptoms such as chronic pelvic pain or subfertility. Several surgical and medical therapies are available to manage symptoms, but a cure has yet to be determined which can be attributed to the incomplete understanding of disease pathogenesis. Sampson's theory of retrograde menstruation is a widely accepted theory describing how shed endometrial tissue can enter the peritoneal cavity, but other factors are likely at play to facilitate the establishment of endometriosis lesions. This review summarizes literature that has explored how dysregulation of menstruation can contribute to the pathogenesis of endometriosis such as dysregulation of inflammatory mediators, aberrant endometrial matrix metalloproteinase expression, hypoxic stress, and reduced apoptosis. Overall, many of these factors have overlapping pathways which can prolong the survival of shed endometrial debris, increase tissue migration, and facilitate implantation of endometrial tissue at ectopic sites. Moreover, some of these changes are also implicated in abnormal uterine bleeding and endometrial diseases. More research is needed to better understand the underlying mechanisms driving dysregulation of menstruation in endometriosis specifically and identifying specific pathways could introduce new treatment targets. Analyzing menstrual fluid from women with endometriosis for inflammatory markers and other biomarkers may also be beneficial for earlier diagnosis and disease staging.