The Visual Effect of a Down-Regulation With Dienogest and GnRH Analogues in Endometriosis: Lessons Learned From Two-Step Surgical Approach.

OBJECTIVE: To evaluate the intraoperative visual effect of treatment with GnRH-analogues and Dienogest in endometriosis. DESIGN: Retrospective observational study. SETTING: Every laparoscopy from all the different disciplines in our hospital is documented on video and stored in a database. The study was approved by the local ethics committee. A total of 193 patients with histological proven endometriosis from 2007 to 2021 were included, who underwent 2-step surgical procedure. Indications were endometrioma before CO2-Laser therapy, missing consent because of emergencies or other surgeries from other disciplines, or high active and extended disease. When endometriosis was suspected in a surgery conducted by other disciplines, a gynecological surgeon was called during the surgery. Data and intraoperative videos were reviewed by 2 independent reviewers at one referral center. Only cases with available video of first and second look laparoscopy were included. We excluded patient who had prior hormonal treatment in the last 6 months. Lesions were classified according to the description of Khan et al. Statistical analysis was performed using SPSS (Version 27.0, IBM). Mann-Whitney U test (nonparametric analysis) and χ2 tests were applied. Percentages were calculated for categorical variables and mean and standard deviation were calculated for continuous variables. Significance level was set to p <.05. INTERVENTIONS: Seventy-seven received GnRH-analogues and 116 Dienogest for preoperative hormone down-regulation. The median duration of down-regulation with GnRH-analogues or Dienogest was 3 months. The mean age was 32.3 (SD 6.3) years for GnRH-analogues and 32.6 (SD 6.3) years for Dienogest, p = .619 respectively. The visible intraoperative effect will be demonstrated in the video. CONCLUSION: The effect of a hormonal treatment can be observed macroscopically in endometriosis. This can help to understand the in vivo response to the administrated treatment. This video is showing our past experience, as performing second-look laparoscopy is not state of the art anymore.

Co-Existence of Endometriosis with Ovarian Dermoid Cysts: A Retrospective Cohort Study.

Both endometriosis and ovarian dermoid cysts are benign conditions characterized by the presence of well-differentiated tissues in ectopic locations. The presence and surgical excision of these entities can potentially impact ovarian reserves, contributing to reduced chances of future pregnancy. The objective of our study is to investigate the bidirectional association between endometriosis and ovarian dermoid cysts, as well as to analyze the clinical characteristics of patients diagnosed with both conditions. A retrospective cohort study was conducted, including women who underwent laparoscopy and received histological diagnoses of endometriosis and/or dermoid cysts between 2011 and 2019 at the Cantonal Hospital of Schaffhausen. We identified 985 women with endometriosis and 83 women with ovarian dermoid cysts. Among these groups, 22 women presented with both endometriosis and ovarian dermoid cysts. The majority of the above patients had endometriosis stage rASRM I-II (72.7%), with peritoneal endometriosis being the most common phenotype of endometriosis (77.2%). Out of the 14 patients with a desire for future pregnancy, the majority (11/14, 78.5%) had an EFI score of 7-8. The prevalence of bilateral ovarian dermoid cysts was higher in women with both ovarian dermoid cysts and endometriosis in comparison to women with ovarian dermoid cysts without endometriosis (18% vs. 6.5%). Our study revealed that 26.5% of women with ovarian dermoid cysts also had endometriosis, a notably higher prevalence than observed in the general population. Clinicians should be aware of this co-existence, and preoperative counseling should be an integral part of the care plan for affected individuals, where the potential risks and the available options for fertility preservation should be discussed in detail.

Is Conception by Means In Vitro Fertilization Associated With Increased Risk of Antenatal Anxiety and Depression?

Objectives Mental health during pregnancy is a very important public health issue with negative effects on both maternal and child outcomes. The aim of our study is to examine the possible association between conception via in vitro fertilization (IVF) and anxiety or depression during the third pregnancy trimester in the Greek population during the years of financial crisis. Materials and Methods This single-center prospective cohort study was conducted in a tertiary university hospital during the period 2017-2018. Pregnant women attending the Antenatal Care Program between 30th-32nd gestational week were asked to complete Hamilton Anxiety Rating Scale (HAM-A) and Beck Depression Inventory (BDI). A propensity score match for 10 variables was conducted in a 1:3 ratio. Results Of the 521 eligible patients, 446 women were included in our study. Four hundred fourteen of them conceived spontaneously, and 32 via IVF. After propensity score matching, 76 remained in the analysis, of whom 57 conceived spontaneously and 19 with IVF. The IVF group had a higher rate of anxiety (18.8%) and a lower rate of depression (9.4%) than the spontaneous conception group (13.5% and 13.5%, respectively), but the differences were not statistically significant before and after propensity score matching.  Conclusion Our study showed that pregnancies after IVF had a higher incidence of antenatal anxiety and a lower incidence of antenatal depression in comparison to pregnancies that were conceived naturally, although the differences did not reach statistical significance.

Treatment after endometrioma recurrence: a narrative review.

INTRODUCTION: Ovarian endometrioma is a common subtype of endometriosis with a prevalence between 17 and 44%. The reported average recurrence of endometrioma after surgical management is 21.5% after 2 years and 40-50% after 5 years. The aim of this narrative review was to summarize the existing literature focusing on treatment options after endometrioma recurrence in order to provide an evidence-based approach for the clinical practice. EVIDENCE ACQUISITION: Three electronic databases (MEDLINE, EMBASE and Cochrane) were searched until September 2022 for eligible studies. EVIDENCE SYNTHESIS: The available studies showed that repeated surgery has a negative impact on ovarian function, without improving the fertility outcomes. Transvaginal aspiration as an alternative option for surgery has a high rate of recurrence, which varies from 8.20 to 43.5% depending on the technique used and on the study population. Pregnancy related outcomes were similar between transvaginal aspiration groups and no intervention groups in patients with endometrioma recurrence. Regarding medical treatments, only four studies were found, showing that progestins reduce the pain and the diameter of the ovarian cyst. CONCLUSIONS: Recurrent endometrioma is a challenging condition which could be encountered during the care of women with endometriosis. The decision about the treatment-strategy has to be individualized considering family planning status, age, ovarian reserve and transvaginal ultrasound findings. Well-designed randomized clinical trials are needed to export safer conclusions about the most appropriate treatment in each specific condition after endometrioma recurrence.

The immunohistochemical expression of GPER and classical sex hormone receptors differs in adenomyosis and eutopic endometrium.

G protein-coupled estrogen receptor (GPER) has been found to be an important key regulator in the homeostasis of sex hormone-dependent human cells. The aim of this study was to compare the expression of GPER, estrogen receptor alpha (ER-α), estrogen receptor beta (ER-ß) and progesterone receptor (PR) in adenomyosis, eutopic endometrium from the same patients, and eutopic endometrium from patients without adenomyosis. Immunohistochemical analysis of GPER, ER-α, ER-ß and PR was performed to assess the expression levels on samples of hysterectomies using tissue microarrays. 73 adenomyotic tissue probes and corresponding eutopic endometrial specimens, as well as 48 samples of eutopic endometrial control specimens from patients without adenomyosis were included in this study. Mean age of the women with adenomyosis was 51.7 (SD ± 11.1) and 65.8% were premenopausal. We found a higher nuclear stromal expression of GPER in eutopic endometrium of patients with adenomyosis in comparison to control endometrium (p < 0.001). Comparing adenomyosis to eutopic endometrium of patients with adenomyosis and to control, there was a lower expression of nuclear GPER in epithelial cells (p < 0.001 and p = 0.048, respectively). Lower epithelial nuclear ER-α in adenomyosis and higher epithelial nuclear ER-ß in eutopic endometrium of patients with adenomyosis was found in comparison to control endometrium (p = 0.008 and p = 0.017, respectively). This study showed a significant difference in the immunohistochemical expression of GPER in adenomyosis compared to eutopic endometrium of the same patients and to endometrium of control group. GPER in adenomyosis may be a potential therapeutic target for selective agonists and antagonists.

Effects of vitamin D supplementation in endometriosis: a systematic review.

BACKGROUND: There is a growing body of human, animal and in vitro studies on vitamin D (vit D) substitution in endometriosis. The aim of this systematic review is to critically appraise and qualitatively synthesize the results of the available studies that examine the supplementation of vit D for endometriosis treatment. METHODS: A systematic search of the literature was conducted in four electronic databases (Medline, Cochrane, Scopus, Embase) and grey literature for original research articles on humans, animals and in vitro models published in any language. RESULTS: Four human studies, four animal studies and four in vitro studies were included. Quantitative synthesis of human studies showed no significant effect of vit D intake for dysmenorrhea (2 studies, 44 vit D vs 44 placebo, mean -0.71, 95% CI -1.94, 0.51) and non-cyclic pelvic pain (2 studies, 42 vit D vs 38 placebo, mean 0.34, 95% CI -0.02, 0.71). Regarding reproductive outcomes in women with endometriosis after in vitro fertilization, the only available study showed no differences between women taking vit D and women taking placebo. Three of the four included animal studies showed regression of endometriotic implants when treated with vit D. The in vitro studies demonstrated that vit D decreases invasion and proliferation of endometriotic lesions without affecting apoptosis. CONCLUSIONS: Although in vitro and animal studies suggest regression of the endometriotic implants and decrease of invasion and proliferation after vit D supplementation, this was not reflected in the results of the meta-analysis, which showed no benefit of vit D supplementation in patients with endometriosis and dysmenorrhea or non-cyclic pelvic pain as well as on the outcome of IVF treatment. However, given the heterogeneity and the diversity of the available studies, more research is required to shed light on the role of vit D supplementation in women with endometriosis.

Intraoperative Appearance of Endosalpingiosis: A Single-Center Experience of Laparoscopic Findings and Systematic Review of Literature.

Background: Endosalpingiosis is assumed to be the second most common benign peritoneal pathology after endometriosis in women. Although recent studies indicate a significant association with gynecologic malignancies, many underlying principles remain unclear. This work aimed to systematically describe the intraoperative appearance of endosalpingiosis. Methods: Data and intraoperative videos of patients with histologically verified endosalpingiosis were retrospectively reviewed. The main outcome measures were macroscopic phenotype and anatomical distribution. Additionally, a systematic review searching PubMed (Medline) and Embase was conducted. Results: In the study population (n = 77, mean age 40.2 years (SD 16.4)), the mean size of lesions was 3.6 mm and the main visual pattern was vesicular (62%). The most frequent localization was the sacrouterine ligaments (24.7%). In the systematic review population (n = 1174 (210 included studies overall), mean age 45.7 years (SD 14.4)), there were 99 patients in 90 different studies with adequate data to assess the appearance of the lesions. The mean size of the lesions was 48.5 mm, mainly with a cystic visual pattern (49.5%). The majority of the lesions affected the ovaries (23.2%), fallopian tubes (20.4%), or lymph nodes (18.5%). Comparing this study to the literature population, the main differences concerned the size (p < 0.001) and main visual patterns (p < 0.001) of lesions. Conclusions: The usual intraoperative findings of endosalpingiosis appeared less impressive than described in the literature. In our study population, lesions of a few millimeters in size with a vesicular appearance were mostly seen, most frequently in the sacrouterine ligament area. Intraoperative recognition by the gynecologic surgeon and histologic diagnosis should play an important role in further understanding this entity, scientifically and clinically.

Prospective Multicenter Trial Assessing the Impact of Positive Peritoneal Cytology Conversion on Oncological Outcome in Patients with Endometrial Cancer Undergoing Minimally Invasive Surgery with the use of an Intrauterine Manipulator : Positive Peritoneal Cytology Conversion and Its Association with Oncological Outcome in Endometrial Cancer.

BACKGROUND: Minimally invasive surgery is the standard approach in early-stage endometrial cancer according to evidence showing no compromise in oncological outcomes, but lower morbidity compared with open surgery. However, there are limited data available on the oncological safety of the use of intrauterine manipulators in endometrial cancer. PATIENTS AND METHODS: This prospective multicenter study included patients with endometrial cancer undergoing laparoscopic staging surgery with the use of an intrauterine manipulator. We obtained three different sets of peritoneal washings: at the beginning of the surgical procedure, after the insertion of the intrauterine manipulator, and after the closure of the vaginal vault. The rate of positive peritoneal cytology conversion and its association with oncological outcomes was assessed. RESULTS: A total of 124 patients were included. Peritoneal cytology was negative in 98 (group 1) and positive in 26 (group 2) patients. In group 2, 16 patients presented with positive cytology at the beginning of the surgery (group 2a) and 10 patients had positive cytology conversion during the procedure (group 2b). Recurrence rate was significantly different among the study groups, amounting to 9.2%, 25.0%, and 60.0% for groups 1, 2a, and 2b, respectively (p < 0.001). Group 1 showed the best recurrence-free and overall survival, followed by group 2a, while patients in group 2b had the worst oncological outcomes (p = 0.002 and p = 0.053, respectively). Peritoneal cytology was an independent predictor of recurrence and death on multivariable analysis. CONCLUSION: A total of 8.1% of patients with endometrial cancer undergoing minimally invasive surgery with intrauterine manipulation showed positive peritoneal cytology conversion associated with significantly worse oncological outcome.

Superficial papilloma of the ovary.

Superficial papilloma of the ovary is a rare benign ovarian finding, which was first described back in 1895. Here, we present the intraoperative and histological findings of a superficial papilloma of the ovary in a 59-year-old patient.

Management of venous thromboembolism in pregnancy.

Venous thromboembolism (VTE) in pregnancy, consisting of deep venous thrombosis (DVT) and pulmonary embolism (PE), is a major factor of maternal mortality. Several patient-specific risk factors along with the physiologic changes of pregnancy promote a state of hypercoagulability in pregnant women. Detailed assessment of all pregnant women can establish a risk profile that would guide clinical decisions, and balance potential therapeutic benefits with side effects. Differentiating between physiologic changes of pregnancy and symptoms of VTE can be challenging and warrants meticulous clinical evaluation. Timely and accurate diagnosis of VTE with proper imaging is essential for its management, and systemic anticoagulation remains the cornerstone of VTE prevention and therapy. Furthermore, advanced invasive treatment options such as inferior vena cava filters and thrombectomy can be considered for complex cases. Importantly, the risk of systemic anticoagulation should be balanced against the risk of VTE-associated morbidity and mortality for mother and fetus, and an informed decision should be made. In this review, we present an up-to-date overview of VTE management in pregnancy and the postpartum period.

How and where to expect endosalpingiosis intraoperatively.

OBJECTIVE: To describe the anatomical distribution and intraoperative morphology of endosalpingiosis. DESIGN: Retrospective observational video study. SETTING: Data and intraoperative videos were reviewed by two independent reviewers at one referral center. The study was approved by the local ethics committee. PATIENT(S): A total of 77 patients with histologically proven endosalpingiosis from 2007-2020. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The primary endpoints were anatomical distribution and macroscopic phenotype. The secondary endpoints were demographic and clinical characteristics as well as associated diseases. RESULT(S): Of the 77 patients with endosalpingiosis, the mean age was 40.2 years (standard deviation, 16.4 years), mean body mass index 24.1 kg/m2 (standard deviation, 5.7 kg/m2), 59.7% (n = 46) were nulligravide, 70.1% (n = 54) nulliparous, 22.1% (n = 17) suffered of infertility, and 53.2% (n = 41) had at least one previous abdominal or vaginal surgery. Endometriosis was associated in 53.2 % (n = 41) and malignancies in 28.6% (n = 22, 7 endometrial cancers, 1 uterine carcinosarcoma, 8 borderline ovarian tumors, 5 epithelial ovarian cancers, and 1 yolk sac tumor of the ovary). Anatomic distribution and varying intraoperative phenotypes were demonstrated in the video presentation. CONCLUSION(S): In the majority of this population, endosalpingiosis was located in the pelvis. The higher prevalence of specific gynecologic tumors is consistent with previous results. In phenotype, most lesions appear to be less spectacular than prominent in the literature. For further studies on the relevance as a risk factor for malignancy and consequently clinical recommendations, sound knowledge about endosalpingiosis of laparoscopists as initial diagnosticians is crucial.

Treatment of endometriosis: a review with comparison of 8 guidelines.

BACKGROUND: Endometriosis, the presence of endometrial-like tissue outside the uterus, is a common clinical entity between women of reproductive age, with a prevalence of about 10%. Due to the variety of endometriosis-associated symptoms, a great variety of treatments have been implemented. The aim of this review is to give an overview on therapeutical approaches of eight national and international widely used guidelines. METHODS: Six national (College National des Gynecologues et Obstetriciens Francais, National German Guideline (S2k), Society of Obstetricians and Gynaecologists of Canada, American College of Obstetricians (ACOG) and Gynecologists, American Society for Reproductive Medicine (ASRM) and National Institute for Health and Care (NICE) and two international (World Endometriosis Society, European Society of Human Reproduction and Embryology) guidelines are included in this review. CONCLUSION: All the above-mentioned guidelines agree that the combined oral contraceptive pill, progestogens are therapies recommended for endometriosis associated pain. Concerning infertility, there is no clear consensus about surgical treatment. Discrepancies are also found on recommendation of the second- and third-line treatments.

[Endosalpingiosis - an Irrelevant Incidental Finding During Laparoscopy?] / Endosalpingiose ­ ein irrelevanter laparoskopischer Zufallsbefund?

Endosalpingiosis - an Irrelevant Incidental Finding During Laparoscopy? Abstract. Endosalpingiosis refers to the ectopic presence of tubal epithelium. However, this incidental finding received little attention, although it is the second most common benign peritoneal pathology in women following endometriosis. In contrast to endometriosis, endosalpingiosis shows an increase in prevalence with age beyond the menopause. Furthermore, it does not appear to be chronically inflammatory and, according to research to this date, does not cause chronic pain or infertility. Recent epidemiological and molecular pathological studies show a significantly higher incidence of ovarian and endometrial tumors in women with endosalpingiosis. These correlations have not been conclusively clarified. Generally accepted clinical recommendations for the detection of endosalpingiosis do not yet exist. In order to better understand the disease value of endosalpingiosis and its oncological correlations, this entity should be brought to the attention of surgical gynecology and involved pathology.

Leptin concentrations in endometriosis: A systematic review and meta-analysis.

INTRODUCTION: Endometriosis is an inflammatory condition, affecting mainly women of reproductive age. Leptin is a regulator of food intake and energy expenditure, posing pleiotropic actions, and regulating immunity and fertility. The aim of this study was to systematically review the literature regarding leptin concentrations in biological fluids and tissues of women with endometriosis, and to investigate and propose a possible role of leptin in the pathophysiology of endometriosis. MATERIALS AND METHODS: A systematic search of the literature was conducted in two electronic databases (MEDLINE, COCHRANE) and grey literature for original research articles on humans, published in any language. RESULTS: Twenty-nine studies with 1291 women with endometriosis and 1664 controls were included in the systematic review. Peritoneal fluid and follicular fluid leptin concentrations were higher in endometriosis compared with control group [mean difference (MD) 7.10, 95 % confidence interval (CI) 4.76 to 9.44 ng/mL, 18 studies), (MD 1.35, 95 % CI 0.54-2.17 ng/ml, 2 studies) respectively. No differences were evident in serum (MD 0.92, 95 % CI -0.84 to 2.68 ng/mL, 12 studies) or plasma (MD -0.95, 95 % CI -4.63 to 2.72 ng/mL, 3 studies) between the groups. No meta-analysis was conducted for ovarian tissue leptin (2 studies). CONCLUSIONS: This meta-analysis provided evidence for increased leptin concentrations in both peritoneal fluid and follicular fluid of women with endometriosis compared with control; these differences were not present in the serum or plasma. The above results support a potential pathophysiologic role for leptin in the local microenvironment while declines its use as a blood diagnostic marker. Furthermore, we propose a possible role of leptin in the pathophysiology of endometriosis.

Isolated torsion of the fallopian tube in a 16-year-old girl: A case report and review of the literature.

Torsion of the fallopian tube is when the tube twists on the axis created between the infundibulopelvic ligament and the utero-ovarian ligament. It most commonly presents with appendicitis-like symptoms, such as abdominal pain, nausea and vomiting. Because of its rarity and non-specific symptoms, it is usually misdiagnosed initially, which delays therapy, at the expense of the preservation of fertility. This case report of a 16-year-old girl who had never had sexual intercourse presents an example of the misdiagnosis of fallopian tube torsion. The definitive diagnosis was based on laparoscopy. We summarize our experience and provide our conclusions after reviewing the literature.

The expression of histone deacetylase 1, but not other class I histone deacetylases, is significantly increased in endometriosis.

Class I histone deacetylases (HDACs-1-3) play an important role in steroid hormone-dependent gene expression and in modulating cell survival and proliferation. We analyzed their expression in a tissue microarray including 74 endometriosis samples and 30 normal endometrium controls. The mean HDAC-1 immunoreactivity score (IRS ± standard deviation) was 7.6 ± 2.5 in endometriosis and 5.3 ± 2.3 in normal endometrium (P < .001). In contrast, the IRSs of HDAC-2 and -3 were 11.7 ± 0.7 and 11.8 ± 1.1 in endometriosis and 11.6 ± 1.0 and 11.9 ± 0.4 in normal endometrium (P = .7 and P = .2), respectively. Significant correlations were found between HDAC-1 and estrogen (-alpha/-beta) and progesterone receptor expression. In conclusion, HDAC-1, but not HDAC-2/-3, was significantly increased in endometriosis and associated with steroid hormone receptor expression that may reflect interdependence. In context with the literature, specific inhibitors of HDAC-1 may have inhibitory activities similar to those of broad-spectrum HDAC inhibitors and may be clinically tolerated, which would increase their chance as an option in the treatment of endometriosis.

Expression of the G protein-coupled estrogen receptor (GPER) in endometriosis: a tissue microarray study.

BACKGROUND: The G protein-coupled estrogen receptor (GPER) is thought to be involved in non-genomic estrogen responses as well as processes such as cell proliferation and migration. In this study, we analyzed GPER expression patterns from endometriosis samples and normal endometrial tissue samples and compared these expression profiles to those of the classical sex hormone receptors. METHODS: A tissue microarray, which included 74 samples from different types of endometriosis (27 ovarian, 19 peritoneal and 28 deep-infiltrating) and 30 samples from normal endometrial tissue, was used to compare the expression levels of the GPER, estrogen receptor (ER)-alpha, ER-beta and progesterone receptor (PR). The immunoreactive score (IRS) was calculated separately for epithelium and stroma as the product of the staining intensity and the percentage of positive cells. The expression levels of the hormonal receptors were dichotomized into low (IRS < 6) and high (IRS > = 6) expression groups. RESULTS: The mean epithelial IRS (+/- standard deviation, range) of cytoplasmic GPER expression was 1.2 (+/- 1.7, 0-4) in normal endometrium and 5.1 (+/- 3.5, 0-12) in endometriosis (p < 0.001), of nuclear GPER 6.4 (+/- 2.6, 0-12) and 6.8 (+/- 2.9, 2-12; p = 0.71), of ER-alpha 10.6 (+/- 2.4, 3-12) and 9.8 (+/- 3.0, 2-12; p = 0.26), of ER-beta 2.4 (+/- 2.2; 0-8) and 5.6 (+/- 2.6; 0-10; p < 0.001), and of PR 11.5 (+/- 1.7; 3-12) and 8.1 (+/- 4.5; 0-12; p < 0.001), respectively. The mean stromal IRS of nuclear GPER expression was 7.7 (+/- 3.0; 2-12) in endometrium and 10.8 (+/- 1.7; 6-12) in endometriosis (p < 0.001), of ER-alpha 8.7 (+/- 3.1; 2-12) and 10.6 (+/- 2.4; 2-12; p = 0.001), of ER-beta 1.8 (+/- 2.0; 0-8) and 5.4 (+/- 2.5; 0-10; p < 0.001), and of PR 11.7 (+/- 0.9; 8-12) and 10.9 (+/- 2.0; 3-12; p = 0.044), respectively. Cytoplasmic GPER expression was not detectable in the stroma of endometrium and endometriosis. The observed frequency of high epithelial cytoplasmic GPER expression levels was 50% (n = 30/60) in the endometriosis and none (0/30) in the normal endometrium samples (p < 0.001). High epithelial cytoplasmic GPER expression levels were more frequent in endometriomas (14/20, 70%; p = 0.01), as compared to peritoneal (9/18, 50%) or deep-infiltrating endometriotic lesions (7/22, 31.8%). The frequency of high stromal nuclear GPER expression levels was 100% (n = 74/74) in endometriosis and 76.7% (n = 23/30) in normal endometrium (p < 0.001). The frequency of high epithelial nuclear GPER expression levels did not differ between endometriosis and normal endometrium. CONCLUSIONS: The present data indicate a unique GPER expression pattern in endometriosis, especially in endometriomas as compared to the normal endometrium. The overexpression of GPER in endometriotic lesions suggests a potential role for GPER in the hormonal regulation of endometriosis, which should be taken into consideration for future hormonal treatment strategies.

Loss of ARID1A/BAF250a-expression in endometriosis: a biomarker for risk of carcinogenic transformation?

Mutations of the tumor-suppressor gene ARID1A result in the loss of protein expression of the BRG-associated factor 250a (BAF250a), a large subunit of transcription-regulating Human SWI/SNF complexes, which have an important role in the control of cell proliferation and tumor suppression. ARID1A mutations are particularly frequent in endometriosis-associated ovarian clear cell and endometrioid carcinomas, and were recently described as a possible key mechanism and early step in the transformation of endometriosis into cancer. Here, we examined the immunohistochemical expression pattern of BAF250a in a tissue microarray including 74 endometriosis and 30 endometrium samples. Ovarian cancer samples (n=136) served as a control. Epithelial BAF250a expression was assessable in 90/104 (87%) and stromal BAF250a expression in 95/104 (91%) of the endometriosis, and endometrium cases due to lack of adequate tissue in some spots. Complete lack of BAF250a expression was observed in three endometriomas (n=3/20, 15%) and one deep-infiltrating endometriosis sample (n=1/22, 5%), but in none of the peritoneal endometriosis (n=0/16) and eutopic endometrium samples (n=0/30). A comparison of the mean immunoreactivity scores revealed a significantly lower expression rate of BAF250a in endometriomas compared with normal endometrium (P<0.0005), as well as peritoneal (P=0.003) and deep-infiltrating endometriosis (P=0.02). Our data demonstrates that a complete loss of BAF250a expression is observable in some endometriotic lesions, especially in endometriomas. In addition, we report that a partial loss of BAF250a expression is occurring in the form of cell clusters indicating a clonal loss of BAF250a expression in these cells. The loss of expression of the tumor-suppressor protein BAF250a in some endometriomas possibly indicates a risk of malignant transformation in these cases, which could be of importance in the determination of individual treatment strategies. However, its role and value as a prognostic parameter in endometriosis needs to be further studied.