Invasion In Women Research Articles

The prognostic impact of substantial lymphovascular space invasion in women with node negative FIGO stage I uterine carcinoma

ObjectiveSubstantial lymphovascular space invasion (LVSI) is an important predictor of lymph node (LN) involvement in women with endometrial carcinoma. We studied the prognostic significance of substantial LVSI in patients with 2009-FIGO stage-I uterine endometrioid adenocarcinoma (EC) who all had pathologic negative nodal evaluation (PNNE). MethodsPathologic specimens were retrieved and LVSI was quantified (focal or substantial) in women with stage-I EC who had a hysterectomy and PNNE. In addition to multivariate analysis (MVA), recurrence-free (RFS), disease-specific (DSS), and overall (OS) survival was compared between women with focal vs. substantial LVSI. Results1052 patients were identified with a median follow-up of 9.7 years. 358 women (34%) received adjuvant radiotherapy. 907 patients (86.2%) had no LVSI, 87 (8.3%) had focal, and 58 (5.5%) had substantial LVSI. Five-year RFS was 93.3% (95% CI: 91.5–95.1), 76.8% (95% CI: 67.2–87.7) and 79.1% (95% CI: 67.6–95.3) for no, focal, and substantial LVSI(p < 0.0001). There was no statistically significant difference in 5-year RFS, DSS, OS, and in the patterns of initial recurrence between women with focal vs substantial LVSI. On MVA with propensity score matching, substantial LVSI was not independently associated with any survival endpoint compared to focal LVSI, albeit both were detrimental when compared to no LVSI. Age ≥ 60 years and higher grade were predictors of worse RFS, DSS, and OS. Additionally, comorbidity burden was an independent predictor for OS. ConclusionsOur results suggest that substantial LVSI does not predict worse survival endpoints or different recurrence patterns in women with stage-I EC with PNNE when compared to focal LVSI.

Endometrial BMP2 Deficiency Impairs ITGB3-Mediated Trophoblast Invasion in Women With Repeated Implantation Failure.

Repeated implantation failure (RIF) leads to a waste of high-quality embryos and remains a challenge in assisted reproductive technology. During early human placentation, the invasion of trophoblast cells into the decidua is an essential step for the establishment of maternal-fetal interactions and subsequent successful pregnancy. Bone morphogenetic protein 2 (BMP2) has been reported to regulate endometrial receptivity and promote trophoblast invasion. However, whether there is dysregulation of endometrial BMP2 expression in patients with RIF remains unknown. Additionally, the molecular mechanisms underlying the effects of BMP2 on human trophoblast invasion and early placentation remain to be further elucidated. Midluteal phase endometrial samples were biopsied from patients with RIF and from routine control in vitro fertilization followed by quantitative polymerase chain reaction and immunoblotting analyses. Human trophoblast organoids, primary human trophoblast cells, and an immortalized trophoblast cell line (HTR8/SVneo) were used as study models. We found that BMP2 was aberrantly low in midluteal phase endometrial tissues from patients with RIF. Recombinant human BMP2 treatment upregulated integrin β3 (ITGB3) in a SMAD2/3-SMAD4 signaling-dependent manner in both HTR8/SVneo cells and primary trophoblast cells. siRNA-mediated integrin β3 downregulation reduced both basal and BMP2-upregulated trophoblast invasion and vascular mimicry in HTR8/SVneo cells. Importantly, shRNA-mediated ITGB3 knockdown significantly decreased the formation ability of human trophoblast organoids. Our results demonstrate endometrial BMP2 deficiency in patients with RIF. ITGB3 mediates both basal and BMP2-promoted human trophoblast invasion and is essential for early placentation. These findings broaden our knowledge regarding the regulation of early placentation and provide candidate diagnostic and therapeutic targets for RIF clinical management.

The Role of ncRNAs in the Immune Dysregulation of Preeclampsia.

The main complications causing practically 75% of all maternal deaths are severe bleeding, infections, and high blood pressure during pregnancy (preeclampsia (PE) and eclampsia). The usefulness of ncRNAs as clinical biomarkers has been explored in an extensive range of human diseases including pregnancy-related diseases such as PE. Immunological dysregulation show that the Th1/17:Th2/Treg ratio is "central and causal" to PE. However, there is evidence of the involvement of placenta-expressed miRNAs and lncRNAs in the immunological regulation of crucial processes of placenta development and function during pregnancy. Abnormal expression of these molecules is related to immune physiopathological processes that occur in PE. Therefore, this work aims to describe the importance of miRNAs and lncRNAs in immune dysregulation in PE. Interestingly, multiple ncRNAS are involved in the immune dysregulation of PE participating in type 1 immune response regulation, immune microenvironment regulation in placenta promoting inflammatory factors, trophoblast cell invasion in women with Early-Onset PE (EOPE), placental development, and angiogenesis, promotion of population of M1 and M2, proliferation, invasion, and migration of placental trophoblast cells, and promotion of invasion and autophagy through vias such as PI3K/AKT/mTOR, VEGF/VEGFR1, and TLR9/STAT3.

The Prognostic Impact of Substantial Lymphovascular Space Invasion in Women with FIGO Stage I Uterine Endometrioid Carcinoma with Pathologically Negative Nodal Evaluation

Substantiallymphovascular space invasion (LVSI) is an important predictor of lymph node involvement in women with endometrial carcinoma. However, its prognostic significance in women with stage I who had pathologic negative nodal evaluation (PNNE) was not fully evaluated. We aimed to evaluate the prognostic significance of substantial LVSI on recurrence-free (RFS), disease-specific (DSS) and overall survival (OS) in women with FIGO stage I uterine endometrioid adenocarcinoma (EC). Our uterine cancer database was queried for women with stage I EC who had a hysterectomy and PNNE at our institution between 1/1990 and 11/2022. Postoperatively, patients were managed with observation or adjuvant radiation therapy (RT) with pelvic external beam RT or vaginal cuff brachytherapy (VB). Women with synchronous malignancies and those who received adjuvant chemotherapy were excluded. Pathologic specimens were retrieved and LVSI was quantified by Gynecology pathologists (none, focal or substantial). Patients' demographics, surgical and pathologic variables were analyzed. Predictors of RFS, DSS and OS using univariate (UVA) and multivariate analysis (MVA) were studied. One thousand fifty-two patients were identified with a median age of 63 years and median follow-up of 9.7 years. Median number of examined lymph node (LN) were 9 (range 4-18). 907 patients (86.2%) had no LVSI, 87 (8.3%) had focal and 58 (5.5%) had substantial LVSI. In patients with focal LVSI, 32.2% received pelvic RT and 39.1% received VB. In patients with substantial LVSI, 20.7% received pelvic RT and 58.6% received VB.Recurrence was diagnosed in 86 patients (8.2%). While any LVSI was associated with tumor recurrence, there was no significant difference for the site of initial recurrence between patients with focal vs. substantial LVSI. 5-year RFS was 93.3% (95% CI 91.5-95.1), 76.8% (67.2-87.7) and 79.1% (67.6-95.3) for no, focal and substantial LVSI. The 5-year DSS was 97.6% (96.5-98.7), 83.5% (75-93.1), and 90% (81.8-99.9); and 5-year OS was 90.7% (88.7-92.8), 72.8% (62.9-84.2) and 86% (76.2-97.2), respectively. Independent predictors of worse 5-year RFS and DSS include any LVSI, age > 60 years, higher tumor grade. Independent predictors of worse 5- year OS include any LVSI, age > 60, high comorbidity burden, and higher tumor grade. Our large data suggest similar recurrence-free, disease specific and OS for women with stage I uterine endometrioid carcinoma who had pathologically negative nodal evaluation and substantial or focal LVSI. There was no significant difference for the site of initial recurrence between patients with focal or substantial LVSI. Multi-institutional pooled analyses may be needed to validate our results.

The Prognostic Significance of the Depth of Cervical Stromal Invasion in Women With FIGO Stage II Uterine Endometrioid Carcinoma.

The objective of this study was to investigate the prognostic significance of the depth of cervical stromal invasion (CSI) in women with FIGO stage II uterine endometrioid adenocarcinoma (EC). Our database of women with EC was quired for patients with stage II EC. Pathologic slides were retrieved and reviewed by gynecologic pathologists to determine cervical stromal thickness and depth of CSI as a percentage of stromal thickness (%CSI). Kaplan-Meier, univariate, and multivariate analyses were used to compare recurrence-free, disease-specific (DSS), and overall survival (OS) between women who had<50% versus ≥50% CSI. Univariate and multivariate analyses were used to assess other prognostic variables associated with survival endpoints. A total of 117 patients were included in our study who had hysterectomy between 1/1990 and 8/2021. Seventy-nine patients (68%) with <50% and 38 (32w%) with ≥50% CSI. After a median follow-up of 131 months, 5-year DSS was significantly worse for women with ≥50% CSI (78% vs. 91%; P =0.04). However, %CSI was not an independent predictor for any of the studied survival endpoints. Independent predictors of worse 5-year recurrence-free survival and DSS included FIGO grade 3 tumors ( P =0.02) and the presence of lymphovascular space invasion ( P =0.03). Grade 3 tumors were the only independent predictor of worse 5-year OS ( P =0.02). Our results suggest that deep CSI is not an independent prognostic factor for survival endpoints in women with stage II uterine endometroid adenocarcinoma. The lack of independent prognostic significance of the depth CSI needs to be validated in a multi-institutional analysis.

Prediction of Deep Myometrial Infiltration, Clinical Risk Category, Histological Type, and Lymphovascular Space Invasion in Women with Endometrial Cancer Based on Clinical and T2-Weighted MRI Radiomic Features.

To predict deep myometrial infiltration (DMI), clinical risk category, histological type, and lymphovascular space invasion (LVSI) in women with endometrial cancer using machine learning classification methods based on clinical and image signatures from T2-weighted MR images. A training dataset containing 413 patients and an independent testing dataset consisting of 82 cases were employed in this retrospective study. Manual segmentation of the whole tumor volume on sagittal T2-weighted MRI was performed. Clinical and radiomic features were extracted to predict: (i) DMI of endometrial cancer patients, (ii) endometrial cancer clinical high-risk level, (iii) histological subtype of tumor, and (iv) presence of LVSI. A classification model with different automatically selected hyperparameter values was created. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve, F1 score, average recall, and average precision were calculated to evaluate different models. Based on the independent external testing dataset, the AUCs for DMI, high-risk endometrial cancer, endometrial histological type, and LVSI classification were 0.79, 0.82, 0.91, and 0.85, respectively. The corresponding 95% confidence intervals (CI) of the AUCs were [0.69, 0.89], [0.75, 0.91], [0.83, 0.97], and [0.77, 0.93], respectively. It is possible to classify endometrial cancer DMI, risk, histology type, and LVSI using different machine learning methods.

Contrast-Enhanced MRI in Women with Endometrial Cancer: Dynamic Versus Single-Phase Acquisitions.

The 2019 European Society of Urogenital Radiology (ESUR) guidelines for endometrial cancer recommend performing either dynamic contrast-enhanced magnetic resonance imaging (CE MRI) or single-phase CE MRI. However, no study has directly compared these options. Therefore, this study compared dynamic versus single-phase CE MRI for the evaluation of myometrial invasion in women with endometrial cancer. This retrospective, single-institution comparative study was conducted among women with surgically proven endometrial cancer, including 30 consecutive women with single-phase CE MRI and 30 age- and pathologic stage-matched women with dynamic CE MRI. Three readers independently compared dynamic and single-phase CE MRI in terms of the tumor-myometrium signal intensity (SI) difference ratio, depth of myometrial invasion, image quality, and image number. Pathologic findings served as a reference standard for the depth of myometrial invasion. The estimated mean SI difference ratios of dynamic CE MRI and single-phase CE MRI fell within an equivalence margin of 0.05 (90% confidence intervals [CIs] = [-0.0497 to -0.0165], [-0.0226 to -0.0403], and [-0.0429 to -0.0433], respectively, for readers A, B, and C). The area under the receiver operating characteristic curve for the detection of deep myometrial invasion was not significantly different between the acquisitions (P = .3315, P = .3345, and P = .8593, respectively). Single-phase CE MRI showed significantly better image quality than dynamic CE MRI (P = .0143, P = .0042, and P = .0066, respectively), while the median number of images for dynamic CE MRI was 2.4 times higher than that for single-phase CE MRI. Single-phase acquisition may be a better option for CE MRI in women with endometrial cancer than dynamic acquisition.

MRI as an aid to ultrasound in detecting bladder or parametrial invasion in accreta spectrum

Ultrasonography (US) is used for screening and diagnosis of placenta accreta spectrum (PAS) . Magnetic resonance imaging (MRI) has become an aid in confirmation. Our objective was to determine whether there is utility in MRI to detect findings such as parametrial invasion and bladder invasion in women with suspected PAS by ultrasound. We performed a retrospective cohort study of 62 people who underwent a hysterectomy for the management of PAS in a tertiary hospital system. MRI was used only after PAS was suspected by ultrasound. US, MRI, operative and pathology reports were reviewed for the presence or absence of bladder and/or parametrial invasion. Parametrial invasion was defined as extension of the placenta into the lateral pelvic side walls. Data were analyzed, with the reference gold standard being operative findings, using ROC area under the curve, sensitivity, specificity, positive predictive value and negative predictive value. From the study population, 8 people had suspected bladder invasion by US and none with suspected parametrial invasion. Whereas MRI suspected bladder invasion in 12 people and 8 had suspected parametrial invasion. At the time of surgery, bladder involvement was identified in 8 people and parametrial invasion was identified in 2 people. The performance of both MRI and US were similar for bladder involvement with a fair ROC-AUC (Table 1). The imaging modalities together had similar sensitivities except that of US in detecting parametrial involvement. The performance of MRI was better than US at identification for parametrial involvement due to the difficulty in identifying parametrial involvement on US alone. Table 2 compares the agreement of MRI vs. US on bladder and parametrial invasion. In a tertiary care center, among those with suspected PAS by US, the overall addition of MRI to detect the severity, as well as bladder invasion and/or parametrial invasion, has a low detection rate with a high false positive rate.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

The Prognostic Significance of the Depth of Cervical Stromal Invasion in Women with FIGO Stage II Uterine Endometrioid Carcinoma

<h3>Purpose/Objective(s)</h3> To explore the prognostic significance of the depth of cervical stromal invasion (CSI) on survival endpoints in women with FIGO stage II uterine endometrioid adenocarcinoma. <h3>Materials/Methods</h3> A total of 117 patients were included in this retrospective review. Between 1990 and 2021, all patients with FIGO stage II endometrial cancer (EC) underwent hysterectomy and oophorectomy at our institution, with or without lymph node dissection. Patients with synchronous ovarian or breast cancer, as well as those who had undergone adjuvant systemic chemotherapy for EC, were excluded from the study. Pathologic slides were retrieved for these patients and were reviewed by a gynecologic pathologist to determine stromal thickness and the depth of CSI. The depth of CSI was then measured as a percentage of invasion (% CSI) and used in the analysis as a continuous or dichotomous variable (< 50% vs > = 50%). Patients' demographics, pathologic, and treatment characteristics were analyzed using univariate and multivariate analysis to calculate recurrence-free (RFS) and disease-specific (DSS) rates. <h3>Results</h3> The median age for the study cohort was 65 years (range, 34–96), and the median follow-up was 131 months (range, 9–334). A total of 90 patients (77%) had lymph node dissection, with a median of 8 examined lymph nodes (range 0-18). Adjuvant radiation therapy (RT) with pelvic or vaginal cuff HDR brachytherapy, or a combination of the two, was completed in 92 patients (79 percent). The median % CSI was 27% (range, 1-100) with 68% of patients having ≥ 50% CSI. While there was a trend for a worse 5-year RFS and DSS for women with ≥ 50% CSI (69% vs. 83%, p = 0.093) and (78% vs. 91%, p = 0.034), respectively, the depth of CSI was not statistically significant as an independent predictor of 5-year RFS, DSS, or OS. The depth of CSI was not associated with a difference in the recurrence pattern (vaginal cuff, pelvic, paraaortic, or distant). In multivariate analysis, FIGO grade was the only predictor of 5-year OS. FIGO grade and the presence of lympho-vascular space invasion (LVSI) were independent predictors of 5-year RFS and DSS. <h3>Conclusion</h3> Deep cervical stromal invasion does not appear to be an independent predictive factor for survival endpoints in women with stage II uterine endometroid cancer, according to our findings. The presence of LVSI and tumor grade were both independent predictors of recurrence-free and disease-specific survival. Pooled data analysis may be needed to validate our study findings.

Detection of parametrial invasion in women with uterine cervical cancer using diffusion tensor imaging at 1.5T MRI

Purpose: The purpose of this study was to prospectively evaluate the capability of diffusion tensor imaging (DTI) of the lumbosacral plexus to identify parametrial invasion by uterine cervical cancer. Materials and methods: Twenty-seven women with biopsy-proven cervical cancer were prospectively enrolled and underwent DTI at 1.5 TMRI. Fractional anisotropy (FA) values were calculated at the level of right and left L5 and S1 roots. The two sides of each patient were considered independently in two groups, according to the presence or absence of parametrial invasion. Differences between FA values of invaded parametria and those of non-invaded parametria were searched using Student t-test. Receiver operating characteristic (ROC) analysis was performed to identify the cut-off value of FA that yielded best sensitivity, specificity and accuracy for the diagnosis of parametrial invasion. Results: A total of 54 parametria in 27 participants (mean age, 52.9 ± 12 years; age range, 30–81 years) were analyzed. Invasion was present in 37/54 (68%) parametria and absent in 17/54 (31%) parametria. FA was greater in parametrial invasion (mean, 0.321 ± 0.036; range: 0.285–0.357) than in the absence of parametrial invasion (0.292 ± 0.02; range: 0.272–0.312) (P = 0.01). At ROC analysis, best cut-off value of FA for the diagnosis of parametrial invasion was >0.3099 (AUC, 0.681; 95% CI: 0.583– 0.768), yielding 62% sensitivity (95% CI: 50.3–73.64), 73% specificity (95% CI: 50.6–85.27) and 66% accuracy (95% CI: 54.62–73.91). Conclusion: Using >0.3099 as cut off-value for FA of L5-S1 roots, DTI has an accuracy of 73% in the diagnosis of parametrial invasion by uterine cervical cancer.

315 Diagnosis of deep myometrial invasion in women with endometrial cancer: A comparison of 3d ultrasound, 2d ultrasound and MRI

Introduction and aims of the study: This systematic review compares all available data regarding the accuracy of 3D ultrasonography, 2D ultrasonography and MRI in the prediction of deep invasion of the myometrium in adult women diagnosed with endometrial cancer. The aim is to determine whether three-dimensional ultrasound is superior to the other two, more conventional and well-established imaging modalities. Methods: The bibliography used in the making of this review was sought in the MEDLINE/PubMed, Web of Science, Scopus and Wiley Online Library databases and meticulously evaluated according to PRISMA 2020 guidelines.

Immunohistochemical expression of P16 and Ki-67 in uterine cervical neoplasms

To study the expression of Ki-67 and p16 in neoplastic lesions of uterine cervix and to evaluate the prognostic significance of tumour differentiation, histological type, stage and grade, depth of tumour invasion and lymphovascular invasion in women with neoplasia of uterine cervix. This study was performed on 50 biopsies and surgically resected specimens of uterine cervix, which were fixed in 10% formalin, processed, paraffin embedded and cut into 3-5 microns thickness, stained with hematoxylin and eosin stains and immunohistochemical staining by p16 and Ki-67 antibodies was performed and studied. Majority of cases of invasive carcinoma cervix were large cell non-keratinizing squamous cell carcinoma, 58 cases (48.2%). Majority of cases of invasive carcinoma cervix were seen in stage 2B, 40 (40.8%) cases followed by stage 3B, 24 (24.4%) cases. Out of 18 cases of large cell non-keratinizing squamous cell carcinoma, 12 (66.7%) showed 3+ positivity for Ki-67. 7 (53.8%) cases of stage 2A showed 3+ positivity, 3 (23.1%) cases each showed 2+ positivity for p16. 7 (36.8%) cases of moderately differentiated SCC showed 3+ positivity, 4 (21.1%) showed 2+ positivity and 5 (26.3%) showed 1+ positivity of Ki-67. Out of 10 stable patients, 4 (40.0%) showed negative p16 immunoexpression and all the 3 cases (100%) with recurrence showed 2+ positivity and 2 (100%) patients with metastasis showed 3+ positivity. Out of 10 stable patients, 6 (60%) showed negative Ki-67 immunoexpression and all the 3 (100%) cases with recurrence showed 3+ positivity and one each (50.0%) patient with metastasis showed 2+ positivity and 3+ positivity. p16 and Ki-67 immunomarkers are useful as a diagnostic and prognostic tool in cases with recurrence and metastasis, helping in early detection of disease progression.

IPMI: Machine Learning-Aided Identification of Parametrial Invasion in Women with Early-Stage Cervical Cancer

Radical hysterectomy is a recommended treatment for early-stage cervical cancer. However, the procedure is associated with significant morbidities resulting from the removal of the parametrium. Parametrial cancer invasion (PMI) is found in a minority of patients but the efficient system used to predict it is lacking. In this study, we develop a novel machine learning (ML)-based predictive model based on a random forest model (called iPMI) for the practical identification of PMI in women. Data of 1112 stage IA-IIA cervical cancer patients who underwent primary surgery were collected and considered as the training dataset, while data from an independent cohort of 116 consecutive patients were used as the independent test dataset. Based on these datasets, iPMI-Econ was then developed by using basic clinicopathological data available prior to surgery, while iPMI-Power was also introduced by adding pelvic node metastasis and uterine corpus invasion to the iPMI-Econ. Both 10-fold cross-validations and independent test results showed that iPMI-Power outperformed other well-known ML classifiers (e.g., logistic regression, decision tree, k-nearest neighbor, multi-layer perceptron, naive Bayes, support vector machine, and extreme gradient boosting). Upon comparison, it was found that iPMI-Power was effective and had a superior performance to other well-known ML classifiers in predicting PMI. It is anticipated that the proposed iPMI may serve as a cost-effective and rapid approach to guide important clinical decision-making.

The Accuracy of Shear Wave Elastography in the Assessment of Placental Invasion in Women with Placenta Previa

Background: Placenta accreta spectrum is a term which describes abnormal invasion of the placenta into the uterine myometrium. The first line in diagnosis is ultrasonography and magnetic resonance imaging may complement the diagnosis. Aim: The aim of the work is to assess the accuracy of shear wave elastography in predication of placental invasion in women with placental previa.Materials and Methods: This is a prospective cohort study which was conducted in Ain Shams University on 50 women with a diagnosis of anterior placenta previa and history of previous cesarean section who were pregnant at 32 weeks or more and were planned for delivery by elective cesarean section. They were subjected to ultrasonography and elastography study and the diagnosis of placenta accreta spectrum was confirmed/ excluded intraoperatively.Results: Placental separation was normal in 36% of cases, delayed in 46 % of cases, partial in 6% of cases only whereas non separation occurred in 12% of cases. elastrgraphy had a sensitivity of 73.7%, specificity of 90.3%, positive predicting value of 82.4% and negative predictive value of 84.8% in diagnosing cases with abnormal placental invasion while sensitivity, specificity positive and negative predictive value of ultrasonography in diagnosing abnormal placental invasion was 89.5%, 96.8%, 94.4% and 93.8% respectively.Conclusion: Elastography is sensitive and specific but inferior to ultrasonography in evaluating women with suspected placenta accreta spectrum but it may be useful in diagnosis of focal invasion.

Preoperative Serum CA125 and Plasma Fibrinogen Levels as Predictors of Lymphovascular Space Invasion in Endometrial Cancer

Background: Lymphovascular space invasion has been shown to be a predictor of lymph node metastasisand decreased survival in patients with endometrial cancer. Unfortunately, LVSI status is most commonlynot available until after hysterectomy at the time of preparation of the final Pathology report. Therefore;LVSI status represent additional information to be considered in decision making process regarding whetherto perform lymphadenectomy or to deliver adjuvant therapy. Thus, it was important to find biomarkers topredict the risk of LVSI before surgery.Objective: To evaluate the value of serum CA125 and plasma fibrinogen for prediction of lymphovascularspace invasion in women with endometrial cancer.Study Design: A prospective observational cross-sectional study.Settings: was carried out in the Department of Obstetrics and Gynecology/ Baghdad Teaching Hospital, andNursing Home Hospital in Medical City complex, Baghdad, Iraq, over a period of 1 year starting from thefirst of December 2017 to the end of November 2018.Patients and Methods: Fifty-five women with endometrial cancer undergoing surgery were included inthis study. We compared the preoperative level of serum CA125 and plasma fibrinogen with postoperativehistopathological report regarding LVSI, the results were statistically analyzed.Results: (16.4%) of the patients with positive lympho-vascular invasion. CA-125, Fibrinogen, were highlysignificantly increased in patients with positive LVSI. Sensitivity was (88.9%), specificity (95.7%), negativepredictive value (95.0%), positive predictive value (91.0%),and accuracy of the test was (92.3%)whenthe cutoff value for CA125 was (28.75U/ml) while for plasma fibrinogen in cutoff value (317mg/dl)thesensitivity was (100.0%), specificity (95.7%),negative predictive value (100.0%), positive predictive value(95.9%) and the accuracy of the test was (97.8%)Conclusion: The preoperative assessment of serum CA 125 and plasma fibrinogen could be used to predictthe LVSI in endometrial cancer.

Low Red Blood Cell Count as an Early Indicator for Myometrial Invasion in Women with Endometrioid Endometrial Carcinoma with Metabolic Syndrome.

PurposeWe investigated the relationship between metabolic syndrome (MetS) and its components and erythrocyte parameters such as red blood cell count (RBC) and hemoglobin (Hb) levels, and their association with the risk of deep myometrial invasion in endometrioid endometrial carcinoma (EEC).Patients and MethodsA total of 473 women diagnosed with EEC between January 2012 and December 2018 were included in the study. MetS was diagnosed using a modified version of the Chinese Diabetes Society 2004 criteria. Demographic and clinical characteristics were stratified by MetS and compared. Logistic regression analyses were performed to calculate the odds ratios (ORs) of myometrial invasion.ResultsThe prevalence of MetS was 18.8% (89/473). RBC and Hb levels were significantly higher in EEC patients with MetS. RBC and Hb values increased linearly with the number of MetS components. The OR of the MetS risk increased across the RBC quartiles (OR=2.212, 95% confidence interval [Cl]=1.125-4.350, P˂0.05). Among EEC patients with MetS, the OR of deep myometrial invasion increased with the decrease of the RBC quartiles (P=0.037). Similarly, in EEC patients with obesity and hyperglycemia or with ≥2 MetS criteria, the lowest RBC level (Q1) was a risk factor for deep myometrial invasion compared with the reference RBC group (Q4, P˂0.05). However, this trend was not evident in EEC patients without MetS and its components.ConclusionEEC with MetS and its components had higher RBC and Hb levels. The association between the erythrocyte parameters and myometrial invasion differed with MetS. RBC was identified as a risk factor of myometrial invasion in EEC patients with MetS and its components.

Epidermal growth factor promotes stromal cells migration and invasion via up-regulation of hyaluronate synthase 2 and hyaluronan in endometriosis

To investigate the role(s) of hyaluronan synthase 2 (HAS2) and hyaluronan in disease progression of endometriosis and epidermal growth factor (EGF)-induced motility changes of endometriotic cells. A case-control experimental study and invitro primary cell culture study. University hospital-affiliated research centers. A total of 21 women with stage I/II endometriosis, 33 women with stage III/IV endometriosis with endometrioma, and 32 women without endometriosis were included in our study. Serum, eutopic endometrial tissues, and/or ectopic endometriotic tissues were collected. Primary eutopic endometrial stromal cells (EuESCs) and ectopic ovarian endometriotic stromal cells (OvESCs) were isolated and cultured from women with ovarian endometrioma, and then treated with or without EGF. The concentrations of EGF and hyaluronan in serum were analyzed by enzyme-linked immunosorbent assay. The expressions and localizations of EGF receptor (EGFR), phosphorylated-(p)EGFR, HAS2, and hyaluronan receptor CD44 in tissues were examined by immunohistochemistry. The mRNA and protein levels of HAS2 in EuESCs and OvESCs were examined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot, respectively, and the concentrations of hyaluronan in conditioned medium were examined by enzyme-linked immunosorbent assay (ELISA). Cell motility was evaluated by transwell migration/invasion assays. Serum EGF and hyaluronan concentrations were higher in women with stage III/IV endometriosis than in women with stage I/II or without endometriosis. EGFR, pEGFR, HAS2, and CD44 were immunolocalized in eutopic endometrium and ectopic endometriotic lesions, and the expressions of pEGFR and HAS2 were elevated in ectopic endometriotic lesions compared to eutopic endometrium. Treatment with EGF upregulated HAS2 and hyaluronan expression as well as cell migration and invasion in both EuESCs and OvESCs, and pharmaceutical blocking of EGFR abolished these effects. In addition, knockdown of HAS2 by small interfering RNA attenuated both basal and EGF-induced hyaluronan expression and cell motility changes. Notably, ERK1/2 and AKT signaling pathways were shown to be downstream of EGF in regulating HAS2 and hyaluronan expression as well as cell migration and invasion. EGF increased the expression of endometriosis-associated hyaluronan and its synthase HAS2, both of which mediated EGF-induced stromal cell migration and invasion in women with endometriosis.

The value of MRI in management of endometrial hyperplasia with atypia

BackgroundThe value of the magnetic resonance imaging (MRI) in the assessment of women with endometrial hyperplasia and its role in diagnosis of myometrial invasion or coexistence of cancer is not known. This study aimed to evaluate the accuracy and usefulness of MRI in the management of patients diagnosed on endometrial biopsy with complex endometrial hyperplasia with atypia (CEHA).MethodsA retrospective study of 86 cases diagnosed with endometrial hyperplasia with atypia on the initial endometrial biopsy in a tertiary university teaching hospital between 2010 and 2015 was carried out. The MRI accuracy in predicting malignant changes and influence the clinical management was compared among women who had either pelvic MRI, transvaginal ultrasound (TVUS), or no additional imagistic studies.ResultsMRI was performed in 24 (28%) and TVUS in 11 (13%)cases, while 51 (59%) women had no additional imagistic studies. In the group of women with no imaging studies, 26/51 (51%) were surgically treated and 8/26 (31%) were diagnosed with endometrial cancer (EEC) stage 1a. In the group of women who had TVUS, 5/11 (45%) were surgically treated and none was diagnosed with EEC. In the group of women who underwent an MRI examination, 20/24 (83%) were surgically treated. Among these, 11/20 (55%) were diagnosed with EEC, 7 had EEC stage 1a, and 4 had EEC stage 1b. Although MRI was able to identify malignant changes with a good sensitivity (91.7%), it had a low specificity in characterisation of malignant transformation (8%). MRI correctly identified 31% of the stage 1a and 33% of the stage 1b endometrial cancer.ConclusionIn this study, we found a potential diagnostic value of MRI for identifying malignant transformation in patients with CEHA. However, pelvic MRI has a rather weak predictive value of myometrial invasion in women with CEHA and concurrent EEC. The diagnostic and therapeutic benefits of MRI assessment in patients with CEHA need further validation.

Prognostic significance of lymphovascular space invasion in low-risk endometrial cancer.

The purpose of this study was to assess the prognostic significance of lymphovascular space invasion in women with low-risk endometrial cancer. A dual-institutional, retrospective department database review was performed to identify patients with 'low-risk endometrial cancer' (patients having <50% myometrial invasion with grade 1 or 2 endometrioid endometrial cancer according to their final pathology reports) at two gynecologic oncology centers in Ankara, Turkey. Demographic, clinicopathological and survival data were collected. We identified 912 women with low-risk endometrial cancer; 53 patients (5.8%) had lymphovascular space invasion. When compared with lymphovascular space invasion-negative patients, lymphovascular space invasion-positive patients were more likely to have post-operative grade 2 disease (p<0.001), deeper myometrial invasion (p=0.003), and larger tumor size (p=0.005). Patients with lymphovascular space invasion were more likely to receive adjuvant therapy when compared with lymphovascular space invasion-negative women (11/53 vs 12/859, respectively; p<0.001). The 5-year recurrence-free survival rate for lymphovascular space invasion-positive women was 85.5% compared with 97.0% for lymphovascular space invasion-negative women (p<0.001). The 5-year overall survival rate for lymphovascular space invasion-positive women was significantly lower than that of lymphovascular space invasion-negative women (88.2% vs 98.5%, respectively; p<0.001). Age ≥60 years (HR 3.13, 95% CI 1.13 to 8.63; p=0.02) and positive lymphovascular space invasion status (HR 6.68, 95% CI 1.60 to 27.88; p=0.009) were identified as independent prognostic factors for decreased overall survival. Age ≥60 years and positive lymphovascular space invasion status appear to be important prognostic parameters in patients with low-risk endometrial cancer who have undergone complete surgical staging procedures including pelvic and para-aortic lymphadenectomy. Lymphovascular space invasion seems to be associated with an adverse prognosis in women with low-risk endometrial cancer; this merits further assessment on a larger scale with standardization of the lymphovascular space invasion in terms of presence/absence and quantity.

OC08.03: Subjective and objective strategies to assess myometrial invasion and cervical stromal invasion in women with endometrial cancer from the IETA cohort

OC08.03: Subjective and objective strategies to assess myometrial invasion and cervical stromal invasion in women with endometrial cancer from the IETA cohort