Influence of ovarian-sparing surgery and ovariectomy on prognosis in early cervical adenocarcinoma: a systematic review and meta-analysis.

Background: The effect of ovarian-sparing surgery versus ovariectomy on prognosis in early cervical adenocarcinoma is controversial. The aim of this study was to compare the effect of ovary preservation versus ovariectomy on the prognosis of patients with cervical adenocarcinoma. Methods: A literature search was conducted of the PubMed, Excerpta Medica Database, Medline, Central, China National Knowledge Infrastructure databases, and China Science Periodical Database. The subjects of the literature study were patients with cervical adenocarcinoma. The literature compared the prognostic impact of ovary-sparing versus ovariectomy surgery. The Newcastle-Ottawa Scale was used to evaluate the quality of the articles. The Chi-square test was used to test the heterogeneity of the articles, and the random-effects model was used if the results indicated heterogeneity. A subgroup analysis and sensitivity analysis were used to examine the source of heterogeneity. If there was no heterogeneity among the articles, a fixed-effects model was used. Publication bias was evaluated using funnel plots and Egger test. Results: A total of 3,467 patients with stage IA-IB cervical adenocarcinoma from 5 articles were included in the meta-analysis, of whom 995 had ovarian preservation and 1,895 had ovariectomy. There was no statistically significant difference in the 5-year overall survival (OS) between the stage IA-IIB cervical adenocarcinoma patients in the ovariectomy group and the ovarian preservation group (P=0.14). Additionally, there was no heterogeneity among these articles, and no publication bias (P>0.05). There was no significant difference in the 5-year progression free survival (PFS) between the stage IA-IIB cervical adenocarcinoma patients in the ovariectomy group and the ovarian preservation group (P=0.11). Additionally, there was no heterogeneity among these articles, and no publication bias (P>0.05). There was no significant difference in the 5-year disease specific survival (DSS) between the stage IA-IIB cervical adenocarcinoma patients in the ovariectomy group and the ovarian preservation group (P=0.48). Additionally, there was no heterogeneity among these articles, and no publication bias (P>0.05). Conclusions: There was no statistically significant difference in 5-year OS, PFS and DSS between ovarian-sparing surgery and oophorectomy for early-stage cervical adenocarcinoma. High-quality randomized controlled trials are still needed to verify this conclusion.

Screening of prognostic immune genes and establishment of prognostic model of cervical adenocarcinoma based on bioinformatics analysis.

Background: There is currently a lack of clinical models to accurately predict the prognosis of cervical adenocarcinoma. This study aimed to explore the correlation between immune genes and the prognosis of cervical adenocarcinoma patients, and establish a prognostic model. Methods: Transcriptome sequencing data sets and clinical data sets of cervical adenocarcinoma samples were downloaded from the Gene Expression Omnibus (GEO) database. Information about the immune gene was obtained from the ImmPort database. Differentially expressed genes and differentially expressed immune genes were screened in cervical adenocarcinoma tissue and normal cervical group by edgeR package. Differentially expressed immune genes were screened for prognosis-related immune genes by Cox analysis. Taking the immune genes related to prognosis as variables, a prognosis prediction model was established by multivariate Cox regression analysis. Kaplan-Meier analysis and a receiver operating characteristic (ROC) curve were used to test the effectiveness of the model. According to the clinical information and risk score, univariate multivariate Cox analyses were used to screen the independent prognostic risk factors of cervical adenocarcinoma. Results: CXCL9 was an independent prognostic factor of cervical adenocarcinoma [hazard ratio (HR) =0.63; P=0.025]. CGB5 (HR =1.22; P=0.034), CXCL12 (HR =1.33; P=0.023), PTX3 (HR =1.53; P=0.024), and CXCL10 (HR =2.31; P=0.031) were prognostic risk factors for cervical adenocarcinoma. The risk score was calculated as follows: risk score = (0.005 × CXCL10) + (0.076 × CGB5) + (0.061 × CXCL12) + (0.034 × PTX3) + (-0.004 × CXCL9). The prognosis of the low-risk score group was better than that of the high-risk score group (P=0.035). The area under the ROC curve (AUC) of the risk score was 0.713, and the predictive power was good. Multivariate Cox analysis showed that N stage (HR =1.34; P=0.035) and risk score (HR =1.37; P<0.001) were independent risk factors for the prognosis of cervical adenocarcinoma (HR >1; P<0.001). Conclusions: In this study, an immune gene prognosis prediction model for cervical adenocarcinoma was established based on the GEO and ImmPort databases. The prediction performance of the model is good, and the prognosis of patients can be evaluated according to the gene expression, which has clinical practicability.

Identification of lesional attributes of dysmenorrhea severity and the serum antimüllerian hormone levels in women with ovarian endometriomas.

OBJECTIVE: To investigate whether lesional immunostaining of putative biomarkers of recurrence and the extent of lesional and cortical fibroses are correlated with the severity of dysmenorrhea and serum antimüllerian hormone (AMH) levels in women with ovarian endometriomas (OEs). DESIGN: Retrospective cohort study. SETTING: Academic hospital. PATIENT(S): A total of 313 women with histologically confirmed OEs were recruited. Their demographic and clinical information and data on their preoperative AMH levels were collected. Additionally, samples of their lesional tissues and ovarian cortex tissues adjacent to the OE lesions were procured for histologic and immunohistochemistry analyses. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): All OE tissue samples were stained for phosphorylated nuclear factor κB p65 subunit, progesterone receptor isoform B, Slit2, and α-smooth muscle actin. In addition, the extent of lesional and cortical fibroses was quantitated by Masson trichrome staining. We evaluated the relationship between the lesion size; laterality; extent of lesional and cortical fibroses, along with the putative markers of recurrence; and severity of dysmenorrhea and preoperative serum AMH levels in patients with OE. RESULT(S): We found that the extent of lesional fibrosis was positively correlated with the severity of dysmenorrhea but had no impact on the AMH levels. On the other hand, the extent of cortical fibrosis, along with age, was negatively correlated with the AMH levels. CONCLUSION(S): The correlation between lesional fibrosis and the severity of dysmenorrhea and between cortical fibrosis and the AMH levels would call an early intervention once OE is diagnosed or suspected to prevent further pain and diminished ovarian reserve.

The relevance of plasma R-spondin 1 and Slit2 as predictive biomarkers in cervical cancer chemotherapy and radiotherapy.

BACKGROUND: R-spondin 1 (Rspol) and Slit2 have been found to play a vital role in cancer development, and have the potential to act as therapeutic adjuvants to increase tolerance to aggressive chemotherapy and/or radiotherapy. This "proof of concept" study evaluates the role of Rspo1 and Slit2 expression in the clinical outcome of cervical cancer patients. METHODS: Using enzyme linked immunosorbent assays (ELISA), we analyzed Rspo1 and Slit2 levels from patients diagnosed with the International Federation of Gynecology and Obstetrics (FIGO) stage IB1-IIA2 cervical cancer (n=34) who received chemotherapy (CT) and/or radiotherapy (RT) and correlated the data with the acute radiation morbidity scoring criteria. RESULTS: Cervical cancer patients who underwent CT and/or RT showed that neither the level of Rspo1 nor the level of Slit2 changed significantly after the first round of CT (CT1), RT, or the second CT (CT2). However, neurological sensory scores and influence of infection scores were elevated following increasing rounds of therapies. Rspo1 levels correlated negatively with the morbidity score of neutrophils, hemoglobin, platelet, infection score, neurological sensory score, and performance status after CT1, RT, or CT2. We also found that Slit2 levels were negatively correlated with genitourinary, heart, and neurological sensory scores at RT and CT2. CONCLUSIONS: The levels of Rspo1 and Slit2 correlate positively to the tolerance of the patients. In contrast, the levels of Rspo1 and Slit2 showed a negative correlation to the morbidity score of the patients undergoing CT and/or RT. Thus, Rspo1 and Slit2 may be potential predictive biomarkers for patients with cervical cancer receiving CT or RT postoperatively, which supports the current pursuit of the clinical significance of Rspo1 and Slit2.

Impact of different therapies on the survival of patients with stage I-IIA cervical cancer with intermediate risk factors.

BACKGROUND: The aim of this study was to determine the effects of different therapies on patients with cervical cancer (CC) with intermediate risk factors. METHODS: Clinicopathological data of 596 patients diagnosed with stage I-IIA CC at the Obstetrics and Gynecology Hospital of Fudan University between January 2013 and November 2015 were retrospectively reviewed. Of the patients, 500 patients received adjuvant therapy including chemotherapy (CT), radiotherapy (RT), and sequential chemotherapy and radiotherapy (CT + RT). Patients who displayed at least one intermediate risk factor number were screened. RESULTS: The median follow-up was 62 months. The 5-year progression-free survival (PFS) and overall survival (OS) of the entire cohort were 90.4% and 90.9%, respectively. Univariate analysis showed that tumor stage, tumor size, pathological type, lymphovascular space invasion, and numbers of medium risk factors were not risk factors for early-stage CC. Compared with the control group, patients who received CT, RT, or CT + RT showed improved PFS and OS (P<0.05). The RT group had lower PFS and OS than the CT and CT + RT groups (P<0.05). Among the 318 patients with a single intermediate risk factor, 297 patients received CT, RT, and CT + RT benefit from adjuvant therapy (P<0.05). Of the 253 patients with high-risk factors, 220 patients received CT, RT and CT + RT get improved PFS and OS (P<0.05). CONCLUSIONS: Patients who received adjuvant therapy had better postoperative outcomes than those who did not receive adjuvant therapy. Patients had CT alone or CT combined with RT had better efficacy than those had RT alone.

RETRACTED ARTICLE: DGUOK-AS1 promotes the proliferation cervical cancer through regulating miR-653-5p/EMSY.

Statement of RetractionArticle title: DGUOK-AS1 promotes the proliferation cervical cancer through regulating miR-653-5p/EMSYAuthors: Yan A, Chen G, and Nie, J.Journal: Cancer Biology & TherapyDOI: https://doi.org/10.1080/15384047.2020.1775445In the version of DGUOK-AS1 promotes the proliferation cervical cancer through regulating miR-653-5p/EMSY by Anqi Yan, Guanhao Chen and Jichan Nie published online July 13, 2020, the authors noted inconsistencies within Figures 1F, 2B, 2L, and 4E. Upon investigation, it was determined that the images are unable to support the findings of the manuscript and the article should subsequently be retracted.The Authors apologise for any inconvenience caused.

Concurrent Learning Curves of 3-Dimensional and Robotic-Assisted Laparoscopic Radical Hysterectomy for Early-Stage Cervical Cancer Using 2-Dimensional Laparoscopic Radical Hysterectomy as a Benchmark: A Single Surgeon's Experience.

BACKGROUND For early-stage cervical cancers, radical hysterectomy (RH) with pelvic lymphadenectomy has been the standard care. This study compared the learning curves and intra-, peri-, and post-operative outcomes for 3-dimensional laparoscopic RH (3D-LRH) and robotic-assisted (RA)-LRH by a surgeon highly skilled in 2-dimensional (2D)-LRH for treatment of early-stage cervical cancer. MATERIAL AND METHODS Two hundred and thirty-nine patients with early-stage cervical cancer (FIGO stage: Ia2-IIa2) admitted to Shanghai Obstetrics and Gynecology Hospital, Fudan University were recruited into this prospective study: 54, 85, and 100 patients underwent 2D-, 3D-, and RA-LRH, respectively and were followed up. Patients' demographic, clinical, and operative information was retrieved and compared. CUSUM (cumulative summation) analysis using a benchmark derived from previously performed 2D-LRHs. RESULTS Both 3D- and RA-LRH had a steep learning curve. 3D-LRH was superior to 2D- and RA-LRH in terms of significantly shorter operating time. For all approaches, the operating time was associated with the uterus size of the patient and was not affected by other parameters. All approaches of LRH yielded comparable radicality and operative results other than operative time. CONCLUSIONS Both 3D- and RA-LRH approaches had similar radicality, and intra-operative and post-operative complication rates, however, 3D-LRH had the shortest operating time and lowest amount of blood loss. After reaching proficiency, RA-LRH had comparable operating time with that of 2D-LRH, and might be even shorter in cases where surgeon has acquired more experience. In countries where labor costs are low; 3D-LRH might be preferable to 2D- and RA-LRH for early-stage cervical cancer.

The Possible Role of Eukaryotic Translation Initiation Factor 3 Subunit e (eIF3e) in the Epithelial-Mesenchymal Transition in Adenomyosis.

Epithelial-mesenchymal transition (EMT) has been reported to be involved in adenomyosis by promoting cell invasion and fibrogenesis. But few studies have identified critical factors that regulate EMT process during adenomyosis. The eukaryotic translation initiation factor 3 subunit e (eIF3e) protein is a component of the multisubunit eIF3 complex essential for cap-dependent translation initiation. The aim of this study was to investigate whether eIF3e is involved in EMT in adenomyosis. Ectopic endometrial tissue samples were collected from 40 premenopausal women with ultrasonographically diagnosed and histologically confirmed adenomyosis. As controls, endometrial samples were obtained from 40 cycling premenopausal women patients who underwent surgery for benign gynecologic disorders or cervical intraepithelial neoplasia but without endometriosis, adenomyosis, nor uterine fibroids. All tissue samples were subjected to immunohistochemistry analysis of eIF3e, transforming growth factor-ß1 (TGF-ß1), E-cadherin, vimentin, Snail, and proliferating cell nuclear antigen (PCNA). The epithelial component of ectopic endometrium showed significantly reduced immunoreactivity against eIF3e and E-cadherin but elevated immunoreactivity against TGF-ß1, Snail, vimentin, and PCNA as compared with that of control endometrium (all P values <.05), and the difference was not affected by age, parity, or menstrual phase. The eIF3e staining levels correlated negatively with those of TGF-ß1, vimentin, Snail, and PCNA (both P values <.05). These data suggest that decreased eIF3e expression may pave way for EMT in the development of adenomyosis through activating the TGF-ß1 signaling pathway. Our study provided novel insights into the development and treatments of adenomyosis.

Robotic-Assisted Radical Hysterectomy Results in Better Surgical Outcomes Compared With the Traditional Laparoscopic Radical Hysterectomy for the Treatment of Cervical Cancer.

OBJECTIVE: The aim of this study was to compare the surgical outcomes of robotic-assisted radical hysterectomy (RRH) with traditional laparoscopic radical hysterectomy (TLRH) for the treatment of early-stage cervical cancer in a large retrospective cohort of a total of 933 patients. METHODS: We have enrolled 100 patients into the RRH and 833 patients into the TLRH group. The surgical outcomes include operating time, blood loss, transfusion rate, pelvic lymph node yield, hospitalization days, duration of bowel function recovery, catheter removal before and after 3 weeks, conversion to laparotomy, and intraoperative and postoperative complications. Follow-up results were also analyzed for all patients. RESULTS: Both groups have similar patient and tumor characteristics but patients with a larger lesion size were preferably enrolled in the TLRH treatment group. The treatment with RRH was generally superior to TLRH with respect to operating time, blood loss, length of hospitalization, duration of bowel function recovery, and postoperative complications. On follow-up of patients, there were no relapses reported in the RRH group compared with 4% of relapse cases and 2.9% of deaths because of metastasis in the TLRH group. No conversion of laparotomy occurred in the RRH group. No significant difference was found with respect to intraoperative complications and blood transfusion between both groups. CONCLUSIONS: The results from this study suggest that RRH is superior to TLRH with regard to surgical outcome and may pose a safe and feasible alternative to TLRH. The operating time and lymph node yield is acceptable. Our study is one of the largest single-center studies of surgical outcomes comparing RRH with TLRH during cervical cancer treatment and will significantly contribute to the safety of alternative treatment options for patients. Furthermore, the difference detected between TLRH and RRH group is further strengthened by the great expertise of the surgeon performing laparoscopic surgeries.

Quercetin alleviates generalized hyperalgesia in mice with induced adenomyosis.

Adenomyosis is a common gynecologic disorder characterized by the presence of endometrial glands and stroma within the myometrium. The present study investigated the effect of quercetin in neonatal Imprinting Control Region mice with tamoxifen­induced adenomyosis. The body weight and hotplate response latency of all mice was examined at 4, 8, 12 and 16 weeks after birth. The mice dosed with tamoxifen were divided into four groups: high­ or low­quercetin group, valproic acid (VPA) group and untreated group. The group of mice that were neonatally administrated with the solvent only (no tamoxifen), received no treatment and served as a blank control group. After 3 weeks of drug treatment, the potential ability of quercetin to improve the generalized hyperalgesia in mice with induced adenomyosis was evaluated by determining the body weight, pain modulation, examining the myometrial infiltration by histology examination of the uterus and detecting the expression of transient receptor potential cation channel subfamily V member 1 (Trpv­1), phospho (p)­p38 mitogen activated protein kinase p­extracellular signal­regulated kinase (p­ERK) in DRG neurons via immunohistochemistry. The results demonstrated that treatment with quercetin improved the generalized hyperalgesia by extending the hotplate response latency, reduced myometrial infiltration and decreased the expression levels Trpv­1, p­p38 and p­ERK in dorsal root ganglion neurons. The results indicated that quercetin decreases the incidence of hyperalgesia in mice with tamoxifen­induced adenomyosis, and the potential mechanism is through reduced central sensitization, which may be a promising treatment for adenomyosis.

Leonurine Attenuates Hyperalgesia in Mice with Induced Adenomyosis.

BACKGROUND Adenomyosis, defined as the invasion of endometrial glands and stroma into the myometrium, is a common gynecological disorder. In the present study we report on the effect of leonurine on ICR mice with adenomyosis induced by neonatal tamoxifen. MATERIAL AND METHODS After being treated with tamoxifen for 4, 8, and 12 weeks, we assessed body weight and pain modulation in mice in hotplate tests. The mice were divided into 5 groups: a low-dose leonurine treatment group, a high-dose leonurine treatment group, a valproic acid (VPA) treatment group, a vehicle only treatment group, and a blank control group. We evaluated body weight, pain modulation in hotplate tests, and the depth of myometrial infiltration. Immunoreactivity staining of progesterone receptor (PR), nuclear factor-κB phosphorylated-p65 (p-p65), cyclooxygenase-2 (COX-2), and oxytocin receptor (OTR) was evaluated by immunohistochemistry. RESULTS The measurement of the body weight, myometrial infiltration, and pain modulation showed that neonatal tamoxifen treatment led to adenomyosis. Leonurine treatment appeared to decrease hyperalgesia and myometrial infiltration. Immunoreactivity staining showed decreased p-p65, COX-2, and OTR protein expressions. CONCLUSIONS Our results indicate that leonurine attenuates hyperalgesia in mice with induced adenomyosis via down-regulating expressions of p-P65, COX-2, and OTR, and could be beneficial for treating adenomyosis.

BMP4 Cross-talks With Estrogen/ERα Signaling to Regulate Adiposity and Glucose Metabolism in Females.

Similar to estrogens, bone morphogenetic protein 4 (BMP4) promotes the accumulation of more metabolically active subcutaneous fat and reduction of visceral fat. However, whether there is a cross-talk between BMP4 and estrogen signaling remained unknown. Herein, we found that BMP4 deficiency in white adipose tissue (WAT) increased the estrogen receptor α (ERα) level and its signaling, which prevented adult female mice from developing high fat diet (HFD)-induced obesity and insulin resistance; estrogens depletion up regulated BMP4 expression to overcome overt adiposity and impaired insulin sensitivity with aging, and failure of BMP4 regulation due to genetic knockout led to more fat gain in aged female mice. This mutual regulation between BMP4 and estrogen/ERα signaling may also happen in adipose tissue of women, since the BMP4 level significantly increased after menopause, and was inversely correlated with body mass index (BMI). These findings suggest a counterbalance between BMP4 and estrogen/ERα signaling in the regulation of adiposity and relative metabolism in females.

Elevated immunoreactivity against class I histone deacetylases in adenomyosis.

BACKGROUND/AIMS: Adenomyosis is a common condition with a poorly understood pathogenesis. Recent data suggest that it may be an epigenetic disease. This study investigated the expression and localization of class I histone deacetylases (HDACs) in women with and without adenomyosis. METHODS: The ectopic and homologous eutopic endometrium of 50 women with adenomyosis and the endometrium of 18 age- and menstrual phase-matched women without adenomyosis were used for immunohistochemical analysis. Tissue sections were immunostained with HDAC1, -2, and -3. Microscopic evaluation to assess the presence and localization of HDAC1-3 throughout the menstrual cycle in both eutopic endometrial and endometriotic tissues of women with adenomyosis was performed and compared with the normal endometrium. RESULTS: We found that, compared with the normal endometrium, immunoreactivity against HDAC1 and HDAC3 was higher in both the eutopic and the ectopic endometrium. Increased HDAC2 in the eutopic endometrium was found to be associated with the severity of dysmenorrhea. CONCLUSION: Given the potential wide-ranging effect of histone deacetylation on gene expression, these findings suggest that HDACs may be involved in adenomyosis. They also suggest the possibility that HDAC2 may be involved in dysmenorrhea and its severity and that HDACs may be potential therapeutic targets in adenomyosis.

Increased immunoreactivity to SLIT/ROBO1 and its correlation with severity of dysmenorrhea in adenomyosis.

Compared with normal endometrium, SLIT expression was statistically significantly higher in ectopic endometrium from women with adenomyosis, while roundabout 1 (ROBO1) immunoreactivity and microvessel density (MVD) level were statistically significantly higher in both eutopic and ectopic endometrium than normal endometrium. Both SLIT immunoreactivity in ectopic endometrium and MVD in eutopic endometrium were positively correlated with the severity of dysmenorrhea and found to be significant predicators for dysmenorrhea severity in women with adenomyosis.

Elevated immunoreactivity to tissue factor and its association with dysmenorrhea severity and the amount of menses in adenomyosis.

BACKGROUND: Heavy menstrual bleeding and dysmenorrhea are two top complaints from women with symptomatic adenomyosis, yet their etiology is poorly understood. Tissue factor (TF) has been shown to be upregulated in endometriosis and at the endometrial bleeding sites of women with long-term progestin only contraception. We sought to investigate the expression and localization of TF in eutopic and ectopic endometrium of women with adenomyosis and in endometrium of women without adenomyosis. We also sought to determine the relationship, if any, between TF immunoreactivity and the amount of menses, uterus size and severity of dysmenorrhea. METHODS: We retrieved tissue samples of eutopic and ectopic endometrium from 50 women with adenomyosis and of endometrium from 18 women without adenomyosis. The tissue sections were subjected to immunostaining and microscopic evaluation to assess the presence and localization of TF in both proliferative and secretory phases in both eutopic and ectopic endometrium and normal endometrium. Information on the amount of menses, severity of dysmenorrhea and other information were collected. RESULTS: We found that TF immunoreactivity was significantly increased in both eutopic and ectopic endometrium as compared with normal endometrium. In addition, we found that the elevated TF immunoreactivity is associated with heavy menses and increased severity of dysmenorrhea. CONCLUSIONS: These results suggest that TF is involved in adenomyosis-associated heavy menstrual bleeding and dysmenorrhea and thus may be a potential therapeutic target in treating symptomatic adenomyosis and perhaps also chronic pelvic pain in women with adenomyosis.

Trichostatin A, a histone deacetylase inhibitor, reduces lesion growth and hyperalgesia in experimentally induced endometriosis in mice.

BACKGROUND: The aim of this study was to evaluate the effect of trichostatin A (TSA) in a mouse model of endometriosis on serum tumour necrosis factor alpha (TNFalpha) levels, hotplate latency, lesion size and immunoreactivity to Trpv1, Pkcepsilon and Pgp9.5. METHODS: We used 30 adult female mice, and endometriosis was induced by auto-transplanting pieces of uterus (ENDO) or fat (SHAM) to peritoneum in lower parts of the abdominal and pelvic cavity. Two weeks later, the ENDO group was further divided into two groups randomly: one received TSA treatments and the other received injections of dimethyl sulfoxide, as did the SHAM mice. Four weeks later, all mice were sacrificed. Response latency in hotplate test and serum TNFalpha levels were measured before the surgery, and before and after the treatment, along with the average lesion size and the immunoreactivity to Trpv1, Pkcepsilon and Pgp9.5, in both eutopic and ectopic endometrium and vaginal tissue. RESULTS: We found that mice receiving TSA had a significantly reduced average lesion size as compared with untreated mice, as well as a significant improvement in response to a noxious thermal stimulus. They also had a significantly lower immunoreactivity to Trpv1 in eutopic endometrium, to Pkcepsilon in ectopic endometrium and to Pgp9.5 in vagina. CONCLUSIONS: Endometriosis causes increased central sensitivity to noxious stimuli. Treatment with TSA significantly reduces lesion growth and may relieve pain symptoms in women with endometriosis, indicating that histone deacetylase inhibitors may be a promising therapeutic agent.

Immunoreactivity of oxytocin receptor and transient receptor potential vanilloid type 1 and its correlation with dysmenorrhea in adenomyosis.

OBJECTIVE: We sought to investigate the expression and localization of oxytocin receptor (OTR) and transient receptor potential vanilloid type 1 (TRPV1) in women with and without adenomyosis. STUDY DESIGN: Ectopic and homologous eutopic endometrium from 50 women with adenomyosis and endometrium from 18 women without adenomyosis were used for immunohistochemical analysis of OTR and TRPV1. Microscopic evaluation assessed the presence and localization of OTR and TRPV1 throughout the menstrual cycle in both eutopic endometrial and endometriotic tissues of women with adenomyosis and compared them with normal endometrium. RESULTS: Compared with normal endometrium, immunoreactivity of OTR and TRPV1 were significantly increased in ectopic endometrium. Both OTR and TRPV1 immunoreactivity were positively correlated with the severity of dysmenorrhea and found to be significant predicators for dysmenorrhea severity. CONCLUSION: These findings suggest that OTR and TRPV1 may be involved in dysmenorrhea and its severity in adenomyosis and may be potential therapeutic targets.

Reduced expression and concomitant promoter hypermethylation of HOXA10 in endometrium from women wearing intrauterine devices.

OBJECTIVE: To determine whether prolonged intrauterine device (IUD) usage is associated with decreased HOXA10 expression and increased methylation in the endometrium. DESIGN: Observational study. PATIENT(S): Women wearing IUDs and not wearing IUDs. INTERVENTION(S): Immunohistochemistry of HOXA10 and methylation-specific PCR. MAIN OUTCOME MEASURE(S): Endometrial HOXA10 expression levels and methylation frequency. RESULT(S): The IUD usage was associated with decreased endometrial HOXA10 expression, concordant with higher frequency of HOXA10 promoter hypermethylation. The HOXA10 hypermethylation was associated with the duration of IUD usage, irrespective age, gravidity, parity, and IUD type. CONCLUSION(S): Prolonged IUD use may induce endometrial HOXA10 hypermethylation and reduced expression. These results suggest a possible novel mode of action for IUD, a possibility to rectify the aberrant methylation through pharmacologic means, and a possible noninvasive way for detection of aberrant methylation at HOXA10.

Immunoreactivity of progesterone receptor isoform B, nuclear factor kappaB, and IkappaBalpha in adenomyosis.

Compared with normal endometrium, progesterone receptor isoform B (PR-B) and IkappaBalpha immunoreactivity were statistically significantly reduced in ectopic as well as eutopic endometrium from women with adenomyosis while nuclear p65, p50, and p52 immunoreactivity were statistically significantly increased in ectopic and eutopic endometrium. Nuclear p65 immunoreactivity was positively associated with heavier menses, and decreased PR-B and increased nuclear p65 immunoreactivity in ectopic endometrium were statistically significantly associated with the severity of dysmenorrhea in women with adenomyosis.