Пролиферативные процессы эндометрия у пациенток в постменопаузе и стероидный транскриптом мононуклеаров периферической крови. Есть ли связь?

The limited efficacy of hormone therapy for endometrial proliferative process (EPP) in postmenopausal patients and its side effects on the immune system functionalities have not been studied in detail. Here we assess the feasibility of hormone therapy for EPP in postmenopausal patients through evaluation of estradiol and progesterone receptor gene expression in endometrial tissue and peripheral blood mononuclear cells (PBMC). The study enrolled 92 postmenopausal patients with EPP, including 37 pts with glandular-fibrous polyps, 7 pts with non-atypical endometrial hyperplasia (EH), 8 pts with atypical endometrial hyperplasia (AEH), 31 pts with moderately differentiated adenocarcinoma and 9 pts with highly differentiated adenocarcinoma. The PBMC isolates and endometrial samples were tested for ER⍺, ERβ, mER, PRA, PRB, mPR and PGRmC1 expression by reverse real time polymerase chain reaction (RT–PCR). Differential changes in PBMC receptor profiles upon in vitro exposure to progesterone or mifepristone were determined for patients with endometrial polyps and healthy women. The results indicate elevated expression of ERα, ERβ, PRA, PRB, mPR and PGRmC1 by endometrial tissues in EH and elevated expression of mER, ER⍺ and PRA by PBMC in AEH, apparently reflecting suppressed functionalities of monocytes, macrophages, Т-cells and natural killer cells. Unaltered expression of the studied genes by PBMC in endometrial adenocarcinoma may reflect the incrementing tumor autonomy. In vitro, mifepristone inhibited ER⍺, ERβ, mPR, PGRmC1, PRA and PRB expression in PBMC isolated from patients with endometrial polyps. We suppose that such effects can mitigate the negative influence of sex steroid hormones on immunocompetent cells.

Objective To evaluate the feasibility and application of histopathology diagnosis of endometrial tissues obtained by endometrial cell collector (Jingyou, SAP- 1). Methods One hundred and ninety-three patients whose endometrial lesions should be excluded were selected. First, endometrial tissue were obtained from the patients by Jingyou, then they underwent comprehensive curettage under hysteroscopy. The histopathology diagnosis was performed respectively. The specimen satisfaction rate and diagnostic accuracy was analyzed and compared. Results The specimen satisfaction rate of curettage under hysteroscopy was 95.85% (185/193). The specimens of 8 cases were not satisfied because the tissues were not enough. The specimen satisfaction rate of Jingyou was 82.38% (159/193). The specimens of 34 cases were not satisfied, among whom in 10 cases scratches did not throughout the whole palace antrum, and in 24 cases tissues quality were poor. The endometrial thickness in unsatisfactory specimen by Jinyou was significantly thinner than that in satisfactory specimen: (0.64 ± 0.18) cm vs. (0.97±0.43) cm, and there was statistical difference (P <0.05). The diagnostic accordance rate between Jingyou and curettage under hysteroscopy was 79.87% (127/159). The sensitivity of Jingyou from high to low was 94.19% (81/86) in normal menstrual endometrial, 7/10 in endometrial carcinoma/ atypical hyperplasia, 67.86% (38/56) in endometrial hyperplasia and 1/7 in endometrial polyps. Missed diagnosis of jingyou inluded 2 cases of endometrial carcinoma and 4 cases of endometrial atypical hyperplasia. The misdiagnosed rate of high grade endometrial lesions was 6/16, and the patients were misdiagnosed because the tissues were not enough. Four cases of endometrial atypical hyperplasia had underwent conservative treatment of repeated curettage. Conclusions Application of Jingyou can obtain micro endometrial tissues, and the accordance rate of histopathology diagnosis is high with curettage under hysteroscopy. When the collector makes a comprehensive collection to the uterine cavity specimen, it can accurately screen endometrial carcinoma and atypical hyperplasia. The patients who have endometrial atypical hyperplasia and receive conservative treatment and curettage repeatedly curettage, thin endometrium and ultrasonic highly suspected endometrial polyps, are not recommend to use Jingyou to obtain specimen. When the specimen is not satisfied using the collector, additional hysteroscopy should be performed to avoid misdiagnosis of high grade endometrial lesions. Key words: Biopsy; Pathology; Endometrial cell collector; Screening

To describe the ultrasound features of different endometrial and other intracavitary pathologies inpre- and postmenopausal women presenting with abnormal uterine bleeding, using the International Endometrial Tumor Analysis (IETA) terminology. This was a prospective observational multicenter study of consecutive women presenting with abnormal uterine bleeding. Unenhanced sonography with color Doppler and fluid-instillation sonography were performed. Endometrial sampling was performed according to each center's local protocol. The histological endpoints were cancer, atypical endometrial hyperplasia/endometrioid intraepithelial neoplasia (EIN), endometrial atrophy, proliferative or secretory endometrium, endometrial hyperplasia without atypia, endometrial polyp, intracavitary leiomyoma and other. For fluid-instillation sonography, the histological endpoints were endometrial polyp, intracavitary leiomyoma and cancer. For each histological endpoint, we report typical ultrasound features using the IETA terminology. The database consisted of 2856 consecutive women presenting with abnormal uterine bleeding. Unenhanced sonography with color Doppler was performed in all cases and fluid-instillation sonography in 1857. In 2216 women, endometrial histology was available, and these comprised the study population. Median age was 49 years (range, 19-92 years), median parity was 2 (range, 0-10) and median body mass index was 24.9 kg/m2 (range, 16.0-72.1 kg/m2 ). Of the study population, 843 (38.0%) women were postmenopausal. Endometrial polyps were diagnosed in 751 (33.9%) women, intracavitary leiomyomas in 223 (10.1%) and endometrial cancer in 137 (6.2%). None (0% (95% CI, 0.0-5.5%)) of the 66 women with endometrial thickness < 3 mm had endometrial cancer or atypical hyperplasia/EIN. Endometrial cancer or atypical hyperplasia/EIN was found in three of 283 (1.1% (95% CI, 0.4-3.1%)) endometria with a three-layer pattern, in three of 459 (0.7% (95% CI, 0.2-1.9%)) endometria with a linear endometrial midline and in five of 337 (1.5% (95% CI, 0.6-3.4%)) cases with a single vessel without branching on unenhanced ultrasound. The typical ultrasound features of endometrial cancer, polyps, hyperplasia and atrophy and intracavitary leiomyomas, are described using the IETA terminology. The detection of some easy-to-assess IETA features (i.e. endometrial thickness < 3 mm, three-layer pattern, linear midline and single vessel without branching) makes endometrial cancer unlikely. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

Introduction/Objective In 2014, the WHO simplified the classification of endometrial hyperplasia (EH) into a two-tier system: endometrial hyperplasia without atypia/benign endometrial hyperplasia (BEH) and atypical endometrial hyperplasia (AEH)/endometrioid intraepithelial neoplasia (EIN), as opposed to the 1994 WHO 4-tier scheme. We conducted this study to assess the diagnostic validity of the two-tier scheme in predicting upgrade to endometrioid adenocarcinoma (EA) in our high-risk patient population. Methods Retrospective review from Aug 2009 to August 2019 revealed 144 cases of EH diagnosed on biopsy. The cases were reclassified using the 2014 two-tier scheme to 81 BEH and 63 AEH. The excisional diagnoses, if available, were compared with the initial biopsy results. Results At hysterectomy, 22 AEH (50%) were diagnosed as benign, with no residual AEH, 15 cases were upgraded to EA (34.1%), and 7 had residual AEH (15.9%). Endometrial polyp was identified in 29 cases out of 63 AEH, 24 of which had a follow-up excision. Among those, 6 were upgrade to EA (25%), significantly lower than the upgrade rate of AEH without polyp (45%) (p=0.0344). Conclusion In our high-risk patient population, the likelihood of upgrade to EA at excision of a biopsy-diagnosed AEH is significantly higher than BEH and is in line with what was reported in the literature for other populations. Patients with endometrial polyps were less likely to progress to EA. Our study demonstrated the diagnostic validity of the two- tiered classification in high-risk population and supports the emphasis on cytological atypia.

AimsThis study aims to examine cases identified with endometrial polyp and carcinoma originating from polyps in patients presenting with gynaecological problems, and to highlight the significance of risk factors contributing to malignancy.Materials and methodsThe study comprised 203 patients who visited our clinic between January 2019 and 2024 with various gynaecological problems and were identified with endometrial polyps after a clinical, radiographic, and laboratory assessment. We retrospectively analysed data from 191 benign endometrial polyps and hyperplasia without atypia and 12 patients with endometrial polyps and underlying endometrial hyperplasia with atypia and/or endometrial carcinoma, diagnosed histopathologically after hysteroscopic resection, retrieved from our hospital's electronic archive system.Two hundred three participants were tested in the study, with 191 classifieds with benign tumours and 12 diagnosed with malignant tumours and atypical endometrial hyperplasia (premalignant). Cases were chosen according on consistent criteria for age, BMI, gravida, parity, abortion, educational level, smoking habits, operation history, and co-morbidities. After determining the sample size for the malignant group, patients from the control group were selected to be included in the study. Initially, patients with similar age and BMI distributions were included into the study. Next, the cases were analysed for similarities in gravida, parity, and abortion parameters, and those that matched were chosen. Following this step, the educational status was compared for resemblance, and examples with matching educational status were chosen. Consequently, the study covered a total of 34 patients, with 12 identified with malignant tumours and atypical endometrial hyperplasia (premalignant) and 22 with benign tumours.Two groups of cases were diagnosed with endometrial polyp, and risk factors that may cause the development of endometrial polyp and underlying carcinoma: age, gravida, parity, abortion, education level, smoking, previous operation history, comorbidity, gynaecological complaints, fasting blood sugar, CRP values, haemoglobin, and haematocrit were evaluated in terms of endometrial polyp sizes, endometrial thickness level, and endometrial polyp localization. By examining the pathological risk factors of these cases, particularly during the premenopausal period, the goal is to predict endometrial cancer, the most prevalent gynaecological cancer in women, along with its antecedents, and implement preventive measures proactively.ResultsAge, BMI, gravida, parity, number of abortions, educational status, smoking status, operation history, co-morbidity, and complaint variables did not exhibit a statistically significant difference between the groups (p > 0.05). It was revealed that the FBG level, CRP level, Polyp length and Endometrial thickness level of the malignant group were statistically significantly higher than the benign group (p < 0.01) (p < 0.05). Upon analysing the FBG distribution among groups, it is noted that the ODDS ratio is 10.20 for FBG values of 122.5 and above (95% CI: 1.97 – 52.78). Upon analysing the CRP distribution by groups, it is noted that the ODDS ratio is 231 for CRP values of 9.7 and above (95% CI: 13.15 – 4058.67). Upon analysing the distribution of Polyp length based on groups, it was determined that the ODDS ratio is 13.5 for Polyp lengths of 2.25 and above (95% CI: 2.47 – 73.71). Upon analysing the distribution of EM thickness based on groups, it is shown that the ODDS ratio is 5.25 for EM thicknesses of 11 and above (95% CI: 1.09 – 25.21).ConclusionEndometrial polyps are common benign growths that are typically not seen as cancer precursors but may be linked to cancer in people with advanced age. It is vital to remember that in cases of endometrial polyps, variables such as increasing polyp length, endometrial thickness, fasting glucose level, and elevated CRP levels are significant risk factors for the development of cancer associated with polyps.

The incidence of endometrial carcinoma in patients with atypical endometrial hyperplasia versus atypical endometrial polyp (438)

Levonorgestrel-releasing intrauterine system (LNG-IUS) as an effective treatment option for endometrial hyperplasia: a 15-year follow-up study

Predictive factors of endometrial lesions in patients with abnormal uterine bleeding

Objective. To study the clinical significance of transvaginal sonoelastography (TVSE) in the differential diagnosis of endometrial hyperplasia and carcinoma. Patients and methods. Fifty-four patients with postmenopausal bleeding and/or ultrasound features of endometrial pathology (mean age: 67.8 ± 3.2 years) were examined. The average length of postmenopause was 8.12 ± 3.4 years. The strain index (SI), which was measured automatically, was used as the main criterion of TVSE. Results. The mean SI varied widely depending on the histological type of endometrial pathology: 2.0 (0.8–4.0) in patients with endometrial carcinoma; 1.6 (0.4–3.2) in patients with atypical endometrial hyperplasia; 0.8 (0.30–1.60) in patients with endometrial hyperplasia without atypia; 0.6 (0.5–2.40) in patients with endometrial polyps against the background of mucosal atrophy. A significant difference for SI was found only when comparing the group of patients with carcinoma with other groups, regardless of the morphological type of benign pathology (p &lt; 0.05). Conclusion. TVSE allows to supplement the results of transvaginal ultrasound according to IETA (International Endometrial Tumor Analysis) system and improve the differential diagnosis of endometrial carcinoma with other benign endometrial pathologies. Key words: transvaginal ultrasound, sonoelastography, endometrial carcinoma, endometrial hyperplasia, endometrial polyps, strain index

The aim of this study is to determine the cut-off value for the histopathological evaluation of premalignant-malignant endometrial pathologies from benign pathologies in postmenopausal asymptomatic patients with increased endometrial thickness. This cross-sectional study included a population that included asymptomatic 481 postmenopausal women with an endometrial thickness of more than 5mm in TVU who underwent diagnostic/ operative hysteroscopy and full curettage between January 2015 and January 2018. Demographic characteristics TVU, hysteroscopy findings of patients were recorded. As a result, in the histopathological outcome, 154(3%) women were evaluated as having normal endometrium, 189(39.3%) women as having endometrial polyps, 93(19.3%) women as having endometrial atrophy, and 23(4.6%) women as having endometrial simple hyperplasia, 5(1%) women as having endometrial simple hyperplasia, 17(3.5%) women as having endometrial atrophy and only one (0.1%) woman as having fibroids. In the 187 postmenopausal women with normal diagnostic hysteroscopic evaluation, histopathological findings were: 13(7%) endometrial hyperplasia, 2(1.1%) atypical endometrial hyperplasia, 27(14.4%) endometrial polyps, 4 2.1%) endometrial atrophy, and 2(1.1%) endometrial carcinoma. The endometrial thickness was analyzed with the ROC curve for cutoff value differentiating atypical endometrial hypreplasia/endometrial carcinoma from benign lesions and 10.5 mm was found with 90% sensitivity and 63% specificity. In conclusion, hysteroscopy is highly effective for identifying the endometrium and focal intracavitary pathologies such as polyps, myomas and foreign bodies in women with abnormal uterine bleeding. However, for the diagnosis of endometrial hyperplasia and cancer, hysteroscopic-guided biopsy with uterine curettage seems to be the best method.

Inflammation has an important role in the progression of endometrial carcinoma. The aim of this study is to find the association between neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), and CA125 in endometrial hyperplasia and endometrial carcinoma. The study also focuses on the association of CA125, NLR, and PLR with histopathological parameters in endometrial carcinoma that are of prognostic importance. This is a prospective cross-sectional study on 57 biopsy-proven cases of endometrial hyperplasia and carcinoma conducted over a period of two years. The NLR, PLR, and CA125 were calculated and recorded in all the 57 cases. The 57 cases were divided into three groups: endometrial hyperplasia without atypia group which included 36 cases, endometrial atypical hyperplasia group which included 10 cases, and the endometrial carcinoma group which included 11 cases. Comparison was done between the groups, and parity, NLR, PLR, and CA125 were found to be significant, but patient age and postmenopausal status were not significant. NLR, PLR, and CA125 were found to increase with higher grade, pT-stage, and nodal stage for the endometrial carcinoma cases. NLR, PLR, and CA125 were marginally increased or normal in the case of endometrial hyperplasia without atypia and endometrial atypical hyperplasia, while they were significantly increased in endometrial carcinoma, and also correlated with an increase in grade, pT-stage, and nodal stage. Hence, these can be considered for additional screening as diagnostic, prognostic, and predictive markers in case of abnormal uterine bleeding with endometrial pathology.

In order to investigate the role of the PTEN expression in carcinogenesis and development of endometrial carcinoma and clarify whether and how PTEN and PI3K/Akt pathway relate to endometrial carcinoma, the expression of PTEN and phospho-Akt was detected by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) methods and Western-blot from 24 cases of endometrial carcinoma, 10 cases of endometrial atypical hyperplasia, 10 cases of endometrial hyperplasia, and 10 cases of normal endometrium. SP immunohistochemical methods were used to measure levels of PTEN protein expression in following 5 study groups: 31 cases of endometrium in proliferative phase, 30 cases of endometrium in secretory phase, 71 cases of endometrial hyperplasia, 25 cases of atypical hyperplasia and 73 cases of endometrial carcinoma. Immunostaining score of PTEN was 3.39+/-0.15 in proliferative phase, 1.90+/-0.21 in secretory phase, 3.34+/-0.29 in endometrial hyperplasia, 0.62+/-0.11 in atypical hyperplasia, and 0.74+/-0.19 in endometrial carcinoma, respectively. PTEN mRNA relative value in normal endometrium, endometrial hyperplasia, endometrial atypical hyperplasia, and endometrial carcinoma was 2.45+/-0.51, 2.32+/-0.32, 0.46+/-0.11, and 0.35+/-0.13 respectively. The expression levels of PTEN mRNA and protein in patients with endometrial carcinoma and atypical hyperplasia were significantly lower than in those of proliferative phase and with endometrial hyperplasia. The level of PTEN expression in patients with endometrial carcinoma was significantly related to tissue type (P<0.005), differentiation (P<0.05) and clinical stage (P<0.05), but not to depth of myometrium invasion (P>0.05). Western blot analysis revealed that Phospho-Akt level in PTEN negative cases was significantly higher, and there was a negative correlation between PTEN and phospho-Akt (r=-0.8973, P<0.0001). It was suggested that loss of PTEN expression was an early event in endometrial tumorigenesis. The phosphorylation of Akt induced by the loss of PTEN took part in the tumorigenesis and development of endometrial carcinoma.

Risk of Discovering Endometrial Carcinoma or Atypical Hyperplasia during Hysteroscopic Surgery in Postmenopausal Women

The risk of endometrial hyperplasia (EH) progressing into endometrioid endometrial cancer ranges from 1% for simple EH without atypia (EHWA) to 46.2% for atypical EH (AEH). Differentiation between both entities is crucial to determine optimal management. As preoperative diagnosis of AEH can be difficult, we aimed to establish clusters of immunohistochemical markers to distinguish EHWA from AEH. We studied 13 immunohistochemical markers (steroid receptors, pro/anti-apoptotic proteins, metalloproteinases (MMP), tissue inhibitor of metalloproteinase (TIMP), CD44 isoforms) known for their role in endometrial pathology. Using supervised clustering, we determined clusters of co-expressed proteins which contributed the most in differentiating EHWA from AEH. From 39 tissue samples (17 EHWA and 22 AEH), we found three clusters of co-expressed proteins: Cluster 1 included two proteins (over-expression of estrogen receptor (ER) and under-expression of progesterone receptor (PR) B in AEH compared to EHWA); Cluster 2: an ER, PR A, MMP-2 and TIMP-1 over-expression and a PR B and TIMP-2 under-expression; Cluster 3: over-expression of ER and MMP-7 and under-expression of PR B and TIMP-2. AEH can be accurately distinguished from EHWA using a supervised clustering of immunohistochemical markers. This promising approach could be useful to improve the preoperative diagnosis of EH.

PurposeTo evaluate factors associated with endometrial pathology during tamoxifen use in premenopausal breast cancer (BC) patients.Materials and MethodsWe reviewed the medical records of premenopausal BC patients treated with tamoxifen who underwent endometrial biopsy with or without hysteroscopy. Clinical characteristics were compared between women with endometrial pathology (endometrial hyperplasia or cancer) and those with normal histology or endometrial polyps.ResultsAmong 284 endometrial biopsies, endometrial hyperplasia was diagnosed in 7 patients (2.5%), endometrial cancer was diagnosed in 5 patients (1.8%), normal histology was noted in 146 patients (51.4%), and endometrial polyp was present in 114 patients (40.1%). When comparing women with endometrial cancer (n=5) to women with normal histology, abnormal uterine bleeding was more common (p=0.007), and endometrial thickness was greater (p=0.007) in women with endometrial cancer. Chemotherapy for BC was also more common in patients with endometrial cancer (p=0.037). When comparing women with endometrial polyps and those with endometrial hyperplasia or cancer, the presence of abnormal uterine bleeding was more common in patients with endometrial hyperplasia or cancer (p<0.001); however, tamoxifen duration and endometrial thickness did not differ significantly between the two groups.ConclusionIn premenopausal BC patients treated with tamoxifen, abnormal uterine bleeding, increased endometrial thickness, and chemotherapy for BC were associated with the occurrence of endometrial cancer. These findings may provide useful information for gynecologic surveillance and counseling during tamoxifen treatment in premenopausal BC patients.