Study of immunohistochemical markers in recurrence of endometrial hyperplasia without atypia in women of reproductive age after treatment with progestins
Authors: Khaskhachikh Dmytro , Potapov Valentin , Poslavska Olesandra , Garagulia Irina 
Published: December 2023

ABSTRACT. The high frequency of hyperplastic processes of the endometrium (EН), the lack of proper effectiveness of hormonal therapy, and the possibility of their malignancy place EH among the most relevant issues in modern medicine. The clinical significance of EH lies in the fact that they are one of the most common causes of uterine bleeding and hospitalization of women. It is known that along with hormonal disorders, other activators of proliferative activity, such as growth factors, proliferation and apoptosis markers, and extracellular matrix components, play a significant role in the development of EН.
The study investigated the immunohistochemical markers in the endometrial tissue of reproductive-aged women with endometrial hyperplasia without atypia who were diagnosed with recurrent hyperplasia without atypia after 6 months of continuous therapy with a daily dose of 200 mg of progesterone. The following markers were selected for the study: PR, ER, p21, dcl-2, KI-67, eNOS, cycl-D1, BAX, b-catenin, E-cadgerin і Caspasa3, whose expression was examined by immunohistochemical methods before and after therapy. The control group consisted of women with secretory changes in the endometrium. The expression of receptors for PR, ER, p21, dcl-2, KI-67, eNOS, cycl-D1, BAX, b-catenin, E-cadgerin і Caspasa3 was studied primarily in women with non-neoplastic endometrial lesions (hyperplasia without atypia) and may be of greater significance in predicting the risk of progression and recurrence. Objective. The aim of the study was to determine changes in the expression of immunohistochemical markers in the endometrium in cases of hyperplasia without atypia before and after the use of progesterone therapy, and to identify the most predictive markers for therapy response. Results. The histological examination revealed significant changes in the endometrial biomarkers after therapy in women with no response to the treatment. The expression of receptors in the endometrium after therapy showed the following indicators: ER: a 20 % increase in glandular cells compared to baseline and a 63.3 % increase compared to the control group. In stromal cells, there was a 63.3% increase compared to baseline. PgR: An 85 % decrease compared to baseline. An 85 % decrease compared to the control group. p21: A 114 % increase in glandular cells compared to baseline and a 5% increase in stromal cells. Overall, there was a 29.3 % increase in expression compared to the control group. bcl-2: An 80 % decrease compared to baseline in glandular cells and a 90 % decrease compared to baseline in stromal cells. Ki-67: A 114 % increase compared to baseline in glandular cells and an expression more than 67% higher than the control group. eNOS: A 69 % increase compared to baseline in glandular cells and an 85% increase compared to baseline in stromal cells. Cyclin D1: A 15% increase compared to baseline in both glandular and stromal cells. BAX: A 10 % increase compared to baseline in both glandular and stromal cells. Beta-catenin: Remained stable compared to baseline in both glandular and stromal cells. E-cad: A 50% increase compared to baseline in glandular cells and a 60% increase compared to baseline in stromal cells. Caspasa3: Showed a 76 % increase compared to baseline and an 80 % increase after therapy in stromal cells, which may be associated with increased apoptosis processes. Conclusions. 1. Markers ER, PgR, b-catenin, p21, cyclin D1, Ki-67, Caspase-3 demonstrated differences between the non-glandular endometrium (EH) group and the control group in the glandular component, and ER, PgR, b-catenin in the stromal component (all p<0.05). This provides a basis for their use as primary diagnostic markers. 2. Markers ER, b-catenin, p21, cyclin D1, Ki-67, eNOS showed differences between the NGE group after treatment and the control group in the glandular component, and ER, b-catenin, and eNOS in the stromal component (all p<0.05). This supports their use as primary diagnostic markers. 3. Markers PgR, Ki-67, Caspase- 3, eNOS demonstrated differences between the NGE group before therapy and the control group in the glandular component, and eNOS in the stromal component (all p<0.05). This indicates their potential as primary diagnostic and prognostic markers. 4. Bcl-2 and BAX markers did not show statistically significant differences in the study groups, suggesting their inability to be used individually as diagnostic or prognostic markers for endometrial hyperplastic processes. Interpretation of the expression results of these markers should consider them in conjunction with other indicators.