Deep Myometrial Invasion Research Articles

Endometrial Cancer in 40 Years Old or Younger: A Single Center Experience

Purpose: The purpose of this study was to identify prognostic factors associated with the successful outcome of endometrial cancer (EC) in women aged ≤40 years. Methods: This was a retrospective cohort study. The medical records of all women aged ≤ 40 years with EC diagnosed on endometrial curettage between 1995 and 2020 were reviewed. Patients who underwent hysterectomy and whose final histopathological evaluation was made in our hospital, or who were evaluated by the members of the tumor board and followed up in our hospital, were included in the study. Results: Median follow-up was 79 months (range 9-192). 42 of 44 patients underwent surgical intervention. 33,4%(n: 14) underwent total abdominal hysterectomy (TAH), bilateral salpingo-oophorectomy (BSO), and pelvic paraaortic lymph node dissection (PPLND). 61.9% (n:26) underwent TAH BSO, and PLND. In one patient (2,4 %) only TAH and in the other patient (2,4%) TAH BSO was performed. Medical treatment was administered to 2 patients who desired to preserve their fertility and had grade 1 endometrioid adenocarcinoma without any evidence of myometrial invasion and a comprehensive evaluation showed no evidence of extra-uterine disease. 26 (59,1%) patients had grade 1, 15(34,1%) had grade 2, and 3(6,8%) had grade 3 adenocarcinoma. CA 125 ≥35 IU/ml was statistically associated with lymph node metastasis (p=0,004), ˃ 50% myometrial invasion (p=0,044), and advanced-stage disease (p=0,048). Conclusions: CA 125 ≥35 IU/ml was statistically associated with lymph node metastasis, deep myometrial invasion, and advanced-stage disease in EC patients ≤ 40 years of age.

SGK1 regulated apoptosis in invasive breast carcinoma.

e13061 Background: Worldwide, breast cancer is the most common type of cancers and the presentation of drug resistance is often associated with poor prognosis. Previous studies have shown the mechanism of drug resistance was affected by apoptosis at different levels in the signaling cascades. This article is aimed to explore the relationship between the serum and glucocorticoid-regulated kinase 1 (SGK1) and apoptosis in invasive breast cancer (IBC). Methods: We evaluated the expression of SGK1 in IBC using publicly available data from The Cancer Genome Atlas (TCGA) and Curtis Breast program. TaqMan probe-based qRT-PCR assay and Western Blot analysis were performed to quantitatively detect the expression of SGK1 at RNA and protein levels in the IBC specimens. Clinicopathologic characteristics associated with overall survival were tested by Cox regression. Gene Set Enrichment Analysis (GSEA) was performed to mine the biological pathways involved in IBC pathogenesis related SGK1 regulatory network using MSigDB database. Immunohistochemistry staining (IHC) was used to detect apoptotic markers Fas, Bcl2 and SGK1 in the IBC specimens. Results: Totally 1109 IBC samples with SGK1 expression data were downloaded from TCGA databases for analyzed. SGK1 expression was elevated in normal breast tissues compared with both invasive ductal carcinoma and invasive lobular carcinoma (p < 0.0001). Among them, SKG expression in 112 tumor tissues was significantly lower than that in paracancerous tissues, especially in advanced patients with TNM stage IV. Western Blot and qRT-PCR assay confirmed that SGK1 expression in IBC was distinctly lower than normal. The Kaplan-Meier survival analysis showed that decreased expression of SGK1 was significantly correlated with the clinical stage (p = 0.036). In Curtis Breast program, we further verified SGK1 gene expression was reduced in stage IV than stage I. The univariate analysis demonstrated that clinicopathologic variables associated with poor survival include age, advanced stage, lymph nodes, distant metastasis and deep myometrial invasion. GSEA revealed that apoptosis was differentially enriched when SGK1 was highly expressed. Similarly, TCGA data indicated that the positive rate of SGK1 was higher in Fas positive IBCs, and the same result was also obtained by IHC in the IBC specimens. Conclusions: Expression of SGK1 regulated apoptosis in invasive breast carcinoma, which might be a potential therapeutic target to overcome refractory and drug-resistant breast cancer.

Evaluation of Immuno histochemical Expression of Stem Cell Markers (NANOG and CD133) in Normal, Hyperplastic and Malignant Endometrium

Background: cancer stem cells (CSC) are potential cause for recurrence, metastasis and resistance of tumorsto different therapeutic modalities like hormonal radiotherapy and chemotherapy. We investigated twoCSC markers (NANOG and CD 133) in normal, hyperplastic endometrium and in endometrial carcinoma.Method: A total of 93 formalin fixed paraffin embedded tissue blocks were used for immunohistochemicalexpression of NANOG and CD133 markers. Results: NANOG expression was detected in 88.37% ofendometrial carcinoma cases compared to 15 % of the normal endometrium and to 60% of hyperplasia cases.In endometrial carcinoma, high NANOG expression was significantly correlated with high grade, deepmyometrial invasion, lymph node metastasis and high stage. CD133 was positive in 76.74% endometrialcarcinoma cases and it shows significant correlation with deep myometrial invasion, positive lymph node,positive lymphovascular invasion and high stage. Normal endometrium showed less expression of CD133(only 5%) than hyperplasia and endometrial carcinoma with statistically highly significant difference.Hyperplastic cases with atypia express higher CD133 than those without atypia (6 out of 12 versus 3 out of18). However, this difference was statistically not significant. Conclusion: The cancer stem cell markersNANOG and CD 133 are expressed in high percentage in endometrial carcinoma in comparison to normaland hyperplasia and their expression are positively correlated with aggressive behavior of the tumor.Therefore, inhibition of these markers can be a promising method to stop progression of early cancers.

Detection of deep myometrial invasion in endometrial cancer MR imaging based on multi-feature fusion and probabilistic support vector machine ensemble

The depth of myometrial invasion affects the treatment and prognosis of patients with endometrial cancer (EC), conventionally evaluated using MR imaging (MRI). However, only a few computer-aided diagnosis methods have been reported for identifying deep myometrial invasion (DMI) using MRI. Moreover, these existing methods exhibit relatively unsatisfactory sensitivity and specificity. This study proposes a novel computerized method to facilitate the accurate detection of DMI on MRI. This method requires only the corpus uteri region provided by humans or computers instead of the tumor region. We also propose a geometric feature called LS to describe the irregularity of the tissue structure inside the corpus uteri triggered by EC, which has not been leveraged for the DMI prediction model in other studies. Texture features are extracted and then automatically selected by recursive feature elimination. Utilizing a feature fusion strategy of strong and weak features devised in this study, multiple probabilistic support vector machines incorporate LS and texture features, which are then merged to form the ensemble model EPSVM. The model performance is evaluated via leave-one-out cross-validation. We make the following comparisons, EPSVM versus the commonly used classifiers such as random forest, logistic regression, and naive Bayes; EPSVM versus the models using LS or texture features alone. The results show that EPSVM attains an accuracy, sensitivity, specificity, and F1 score of 93.7%, 94.7%, 93.3%, and 87.8%, all of which are higher than those of the commonly used classifiers and the models using LS or texture features alone. Compared with the methods in existing studies, EPSVM exhibits high performance in terms of both sensitivity and specificity. Moreover, LS can achieve an accuracy, sensitivity, and specificity of 89.9%, 89.5%, and 90.0%. Thus, the devised geometric feature LS is significant for DMI detection. The fusion of LS and texture features in the proposed EPSVM can provide more reliable prediction. The computer-aided classification based on the proposed method can assist radiologists in accurately identifying DMI on MRI.

Grossly unremarkable cervix in endometrial carcinomas: lymphovascular space invasion and microcystic elongated and fragmented pattern may be associated with high incidence of cervical stromal involvement

Accurate staging of endometrial carcinoma is crucial to optimize patients' care. A pivotal parameter that pathologists evaluate to guide staging is the presence of cervical stromal involvement. However, the standard protocol for adequate sampling of the cervix is lacking. A total of 71 grossly unremarkable cervices in hysterectomy specimens with endometrial carcinomas have been studied. Sixty-three (89.7%), five (7.0%), and three (4.2%) were FIGO stage I, II, and III, respectively. Of 71 (8.5%) cases, 6 cases had cervical stromal involvement, among which, 4 (67%) showed endometrioid carcinoma (EC), 1 case of serous carcinoma, and 1 carcinosarcoma. Microcystic elongated and fragmented (MELF) pattern was identified in 12 (16.9%) cases, among which 11 were EC. The presence of MELF pattern was associated with advanced age, deeper myometrial invasion, and advanced FIGO stage. Tumors with lower uterine segment involvement (5/6; 80%), lymphovascular space invasion (4/6; 67%), and MELF pattern (3/6; 50.0%) tended to have cervical stromal involvement. Thus, we provide evidence that the presence of these features in hysterectomy specimens from patients with endometrial carcinoma may warrant extended sampling of the cervix while submitting four representative sections (one section from each quadrant) seems adequate to evaluate for occult cervical stromal involvement in grossly unremarkable cervices in the absence of these features.

Role of brachytherapy in stage III endometrial cancer treated with adjuvant chemotherapy: Identifying factors predictive of a survival benefit

To determine which patients with stage III endometrial cancer receiving adjuvant chemotherapy derive benefit from the addition of vaginal brachytherapy, as stage III is a highly heterogeneous population with substantial variations in practice. Patients with FIGO stage III endometrial carcinoma diagnosed 2004-2016 who underwent at least total hysterectomy and adjuvant multiagent chemotherapy were identified in the National Cancer Database. The primary outcome was overall survival according to receipt of brachytherapy, stratified by histologic type, pathological features, and status of pelvic external beam radiotherapy (EBRT), and analyzed using the Kaplan-Meier method and Cox multivariable regression. In total, 9369 patients were identified (24% stage IIIA, 5% stage IIIB, 71% stage IIIC; 61% endometrioid, 39% nonendometrioid histology), and 28% received brachytherapy. In the endometrioid cohort, brachytherapy was associated with a 5% absolute increase in 3-year overall survival (87% vs. 82%, p < 0.0001), which persisted in multivariable analysis (adjusted hazard ratio 0.74, 95% confidence interval 0.64-0.84, p < 0.0001). The benefit of brachytherapy was greater in patients not also receiving EBRT, and in patients with vaginal/parametrial extension, grade 3 disease, lymphovascular invasion, and/or deep myometrial invasion. In the nonendometrioid cohort, brachytherapy was associated with a significant survival benefit in univariable but not multivariable analysis, regardless of EBRT status or pathological features. Factors predictive of brachytherapy benefit were endometrioid histology and pathological risk factors for local recurrence. Additionally, brachytherapy appeared more beneficial in patients not already receiving pelvic EBRT. Further research is warranted to determine which stage III patients may be best served by brachytherapy, EBRT, or both.

Lymphovascular space invasion in endometrial carcinoma: Tumor size and location matter

ObjectiveTo analyze histological factors possibly associated with lymphovascular space invasion (LVSI) and to determine which of those can act as independent surrogate markers. MethodsRetrospective cohort study performed between January 2001 and December 2014. LVSI was defined as the presence of tumor cells inside a space completely surrounded by endothelial cells. Risk factors evaluated included myometrial invasion, tumor grade, size, location, and cervical invasion. Univariate logistical regression models were applied to study any possible association of LVSI with these factors. Values were adjusted by multivariate logistic regression analysis. ResultsA total of 327 patients with endometrial carcinoma treated in our Centre were included. LVSI was observed in 120 patients (36.7%). Lower uterine segment involvement (OR 5.21, 95% CI:2.6–10.4, p < 0.001) and size ≥2 cm (OR 2.62, 95% CI: 1.14–6.1, p < 0.001) were independent factors for LSVI in multivariate analysis. In univariate analysis, LVSI was a surrogate marker in type 1 tumors with deep myometrial invasion (IB, 51.9% vs. IA, 16.0%; p < 0.001), grade 3 (G3 55.8% vs. G1 16.2%; p < 0.001), size ≥2 cm (37.9% vs. 16.1%, p = 0.005), those with involving the lower segment of the uterus (58.9% vs. 22.5%, p < 0.001) and/or with cervical stromal invasion (65.4% vs. 26.1%, p < 0.001), and in type 2 tumors (61.5% vs. 30.5%, p < 0.001). The use of uterine manipulator did not increase the rate of LVSI (35.5% vs. 40.5%, p = 0.612) as compared to no manipulator use. ConclusionsSize ≥2 cm and involvement of the lower uterine segment are independent factors for LSVI, in type 1 tumors, which can be used for surgical planning. LVSI is also more common in type 1 tumors with deep myometrial invasion, grade 3 and/or cervical stromal invasion, and also in type 2 tumors. The use of a uterine manipulator does not increase LVSI.

MRI to assess deep myometrial invasion in patients with endometrial cancer:A multi-reader study to evaluate the diagnostic role of different sequences

ObjectiveThe identification of deep myometrial invasion (DMI) represents a fundamental aspect in patients with endometrial cancer (EC) for accurate disease staging. It can be detected on MRI using T2-weighted (T2-w), diffusion weighted (DWI) and dynamic contrast enhanced sequences (DCE). Aim of the study was to perform a multi-reader evaluation of such sequences to identify the most accurate and its reliability for the best protocol. MethodsIn this multicenter retrospective study, MRI were independently evaluated by 4 radiologists (2 senior and 2 novice) with a sequence-based approach to identify DMI. The performance of the entire protocol was also evaluated. A comparison between the different sequences assessed by the same reader was performed using receiver operating curve and post-hoc analysis. Intraclass Correlation Coefficient (ICC) was used to assess inter- and intra-observer variability. ResultsA total of 92 patients were included. The performance of the readers did not show significant differences among DWI, DCE and the entire protocol. For only one senior radiologist, who reached the highest diagnostic accuracy with the entire protocol (82,6 %), both DWI (p = 0,0197) and entire protocol (p = 0,0039) were found significantly superior to T2-w. The highest inter-observer agreement was obtained with the entire protocol by expert readers (ICC = 0,77). ConclusionsFor the detection of DMI, the performances of DWI and DCE alone and that of a complete protocol do not significantly differ, even though the latter ensures the highest reliability particularly for expert readers. In cases in which T2-w and DWI are consistent, an unenhanced protocol could be proposed.

What is the predictive value of preoperative CA 125 level on the survival rate of type 1 endometrial cancer?

Background/aim To investigate the utility of preoperative serum cancer antigen 125 (CA 125) levels in type 1 endometrial carcinoma (EC) as a marker for determining poor prognostic factors and survival.Material and methodsAll patients with endometrial cancer, who had been treated between 2012 and 2020, were retrospectively reviewed, and finally, 256 patients with type 1 endometrium carcinoma were included in the study. The relationship between the clinicopathological characteristics, CA 125 level, and survival rates were analyzed. The cut-off value for the preoperative serum CA 125 level was defined as 16 IU/L. Results The median serum CA 125 levels were significantly higher in patients with deep myometrial invasion, lymph node metastasis, lymphovascular space invasion, cervical stromal and adnexal involvement, advanced stage, positive peritoneal cytology, recurrence, and adjuvant therapy requirement. Serum CA 125 cut-off values determined according to clinicopathologic factors ranged from 15.3 to 22.9 IU/L (sensitivity 61%–77%, specificity 52%–73%). The disease-specific survival rate was significantly higher in patients with CA 125 levels < 16 IU/L (P = 0.047).Conclusion The data showed that choosing a lower threshold value for the CA 125 level (16 IU/L) instead of 35 IU/L, could be more useful in type 1 EC patients with negative prognostic factors.

Prognostic value of serum HE4 level in the management of endometrial cancer: A pilot study.

Human epididymis protein 4 (HE4) has shown promising utility as a prognostic biomarker in endometrial cancer. Increased serum HE4 levels may be associated with deeper myometrial invasion, extrauterine disease and poorer prognosis. To evaluate the use of serum HE4 level, compared to and alongside other investigations, to accurately guide management in apparent early-stage endometrial cancer. This is a single-site prospective study of 100 patients with histologically confirmed endometrial cancer. All patients underwent preoperative measurements of HE4 and CA125 levels and a preoperative magnetic resonance imaging (MRI) to assess the depth of invasion, nodal status and tumour size. Correlation was sought between serum HE4 level, CA125 level, MRI findings and intra-operative frozen section with tumour type, grade and stage. While both median HE4 and CA125 levels were higher with worsening clinicopathological features, serum HE4 level showed a more consistent association with high-risk features. Patients with a low-grade biopsy preoperatively and a low HE4 level (<70pmol/L) demonstrated an 86.8% likelihood of having low-risk disease on final histopathology. In comparison, preoperative MRI or intraoperative frozen section alongside a low-grade biopsy demonstrated a similar likelihood of 86.2 and 87.7%, respectively. When used in conjunction with an initial low-grade endometrial biopsy, serum HE4 level demonstrated a similar likelihood to both preoperative MRI and intraoperative frozen section in identifying low-risk disease on final histopathology. As a triaging tool this may be significant given that a preoperative, serum-based assay would likely be the least invasive, least resource-intensive and most cost-effective approach.

Metformin Associates With Aggressive Features of Endometrial Cancer in Women With Type 2 Diabetes.

Preclinical studies on metformin use and endometrial cancer have been promising but epidemiological studies have reported variable results. This study aimed to assess if metformin use is associated with endometrial cancer aggressiveness and survival in women with type 2 diabetes (T2D). This retrospective hospital-based cohort consisted of women with T2D who were treated for endometrial cancer at the Oulu University Hospital, Finland, between 2007 and 2014. The sample size was 121 patients: 58 metformin users and 63 metformin non-users. Intriguingly, type 2 histology, deep myometrial invasion and the presence of lymphovascular invasion were more common in the metformin user group. However, metformin use showed no association with overall survival and progression-free survival. Metformin use was associated with poorer prognostic factors in endometrial cancer patients with T2D.

Tumoral volume measured preoperatively by magnetic resonance imaging is related to survival in endometrial cancer

BackgroundThe aim of the study was to determine if the endometrial tumor volume (TV) measured by magnetic resonance imaging (MRI-TV) is associated with survival in endometrial cancer and lymph nodes metastases (LN+).Patients and methodsWe evaluated the MRI imaging and records of 341 women with endometrial cancer and preoperative MRI from 2008 to 2018. The MRI-TV was calculated using the ellipsoid formula measuring three perpendicular tumor diameters. Tumor myometrial invasion was also analyzed.ResultsHigher MRI-TV was associated with age ≥ 65y, non-endometrioid tumors, grade-3, deep-myometrial invasion, LN+ and advanced FIGO stage. There were 37 patients with LN+ (8.8%). Non-endometrioid tumors, deep-myometrial invasion, grade-3 and MRI-TV ≥ 10 cm3 were the factors associated with LN+. Using a receiver operating characteristic [ROC] curve, the MRI-TV cut-off for survival was 10 cm3 (area under curve [AUC] = 0.70; 95% CI: 0.61–0.73). 5 years disease-free (DFS) and overall survival (OS) was significantly lower in MRI-TV ≥ 10 cm3 (69.3% vs. 84.5%, and 75.4% vs. 96.1%, respectively). MRI-TV was considered an independent factor of DFS (HR: 2.20, 95% CI: 1.09–4.45, p = 0.029) and OS (HR: 3.88, 95% CI: 1.34–11.24, p = 0.012) in multivariate analysis.ConclusionsMRI-TV was associated with LN+, and MRI-TV ≥ 10 cm3 was an independent prognostic factor of lower DFS and OS. The MRI-TV can be auxiliary information to plan the surgery strategy and predict the adjuvant treatment in women with endometrial cancer.

Clinical relevance of oncogenic driver mutations identified in endometrial carcinoma

PurposeEndometrial carcinoma (EC) is a clinically heterogeneous disease characterized by a number of different histological subtypes, and its heterogeneity may be involved in the accumulation of multiple genetic alterations. The aim of this work was to investigate the comprehensive mutational profile of EC tumors, and examine the associations between somatic mutations and clinicopathological features or survival in EC patients. MethodsA total of 100 surgical tumors were obtained from EC patients who had previously undergone surgery. Genomic DNA samples extracted from fresh-frozen tissues were analyzed using the Ion AmpliSeq Cancer Hotspot Panel v2 Kit, covering 50 tumor-related genes. ResultsValidated mutations were detected in 91 of the 100 tumors (91%) and identified in eight of the most frequently mutated genes, namely PTEN (57%), PIK3CA (51%), TP53 (30%), KRAS (23%), CTNNB1 (21%), FBFR2 (13%), FBXW7(10%) and RB1 (9%). PTEN mutations were found to associated with young age (< 60), early-stage, endometrioid histology, non-recurrence and better overall survival (OS). CTNNB1 mutations were associated with young age, endometrioid histology and better OS. On the other hands, TP53 mutations were associated with late-stage, non-endometrioid histology, high-grade, recurrence and worse OS. FBWX7 mutations were associated with late-stage, vascular invasion and lymph node metastasis. FGFR2 mutations correlated with deep (≥ 1/2) myometrial invasion. ConclusionOur comprehensive mutational profile will be useful for understanding and evaluating the molecular characteristics of EC tumors, and may lead to the establishment of novel treatment strategies that improve the survival of patients with EC in the future.

Risk factors for cervical stromal involvement in endometrioid-type endometrial cancer.

The aim of this study was to identify predictors of cervical stromal involvement in women with endometrioid-type endometrial cancer (EEC). A total of 795 patients with EEC who underwent comprehensive surgical staging including pelvic and para-aortic lymph node dissection between January 2007 and December 2018 were retrospectively analyzed. Data including age, menopausal status, serum CA-125 levels, tumor size, lymphovascular space invasion (LVSI), depth of myometrial invasion, positive peritoneal cytology, cervical stromal involvement, histologic grade, recurrence, and follow-up duration were recorded. Median follow up was 49months. Cervical stromal invasion was found in 88 patients. Multivariate analysis revealed that presence of LVSI (hazard ratio [HR] 2, 95% confidence interval [CI] 1.02-4.25, P=0.045), a primary tumor diameter of at least 3cm (HR 3, 95% CI 1.31-7.25, P=0.010), and at least 50% deep myometrial invasion (HR 2.7, 95% CI 1.37-5.41, P=0.004) were independent risk factors for cervical stromal involvement in patients with EEC. Our study results suggest that presence of LVSI, a primary tumor diameter of at least 3cm, and LVSI of at least 50% seem to be independent predictors of cervical involvement in women with EEC.

Importance of pre-operative ultrasound examination and pathological tumour evaluation in the management of women with endometrial cancer

IntroductionEndometrial cancer (EC) is the most common gynaecological malignancy in developed countries. Early and accurate diagnostic assessment is crucial for appropriate treatment planning. Information obtained by pre-operative imaging with transvaginal ultrasound (TVUS) and histological endometrial biopsy assessment is often the cornerstone for further management planning. This study aimed to analyse the accuracy of this diagnostic approach for patient management decisions. Materials and methodsThis single-centre retrospective analysis included all patients with endometrial cancer treated between 2015 and 2019. Pre-operative TVUS staging assessment and histopathological endometrial biopsy examination were compared with the final surgical stage and histopathological diagnosis. ResultsPre-operative and surgical pathological assessment of Type I and Type II tumours was in agreement in 95 % (174/184) and 54 % (12/22) of cases, respectively. The sensitivity and specificity of TVUS assessment of myometrial invasion were 76 % [95 % confidence interval (CI) 66.3–84.2 %] and 81.7 % [95 % CI 73.0–88.6 %], respectively. Diagnostic accuracy was higher for Type I EC (95 %) than Type II EC (54 %). Only presumed ESMO/ESGO/ESTRO risk classification (p < 0.000) and deep myometrial invasion (p < 0.000) were significant for the prediction of lymph node involvement. ConclusionPre-operative TVUS examination and pathological endometrial biopsy evaluation enable moderately accurate assessment of the risk of EC. Efforts should be aimed towards the development of novel and more reproducible methods, such as molecular tumour characterization, to improve the pre-operative assessment of risk in patients with EC.

Value of preoperative HE4 as predictor of advanced disease in endometrioid endometrial cancer.

To explore the predictive value of serum human epididymis protein 4 (HE4) marker in the preoperative prediction of the risk of advanced disease in the endometrioid subtype of endometrial cancer, and its association with poor prognostic factors. In addition, a cut-off value of HE4 was defined to classify patients according to these results. Prospective and multicenter cohort analytical pilot study of patients operated for endometrial cancer at the Miguel Servet University Hospital of Zaragoza (Spain) and the Complejo Universitario of León (Spain) from January 2017 to May 2019. Preoperative serum levels of HE4 were analyzed by clinical and pathologic characteristics. In all, 126 patients were included. A statistically significant association was found between the preoperative HE4 value and node involvement (P=0.008), late-stage disease (P=0.003), high histologic grade (P=0.007), deep myometrial invasion (P=0.001), lymphovascular space invasion (P=0.001), and other pathologic factors. In addition, an HE4 cut-off value (156.4pmol/L) has been determined to predict, preoperatively, which patients will present with early stage disease. The preoperative marker HE4 is a useful tool in the preoperative study of patients with endometrial cancer as it relates to late-stage disease as well as other prognostic factors in the endometrioid subtype of endometrial cancer.

Elevated CA-125 Level and ER-Negative as Prognostic Factors for Ovarian Metastasis in Patients with Endometrial Cancer: A Retrospective Cohort Study.

BackgroundThe utility of cancer antigen 125 (CA-125), estrogen receptor (ER), and progesterone receptor (PR) in evaluation for ovarian metastasis of endometrial cancer has yet to be determined. The purpose of this study was to investigate the incidence and the possible risk factors of ovarian metastasis.Material/MethodsA retrospective study was performed in endometrial cancer patients who accepted surgical intervention of hysterectomy and oophorectomy during 2002–2013 in Sun Yat-sen Memorial Hospital, Sun Yat-sen University, China. Clinico-pathologic characteristics and the possible risk factors were investigated.ResultsA total of 565 patients were identified, of which 5.7% had ovarian metastasis. Univariate analysis and multivariate analysis revealed that deeper myometrial invasion, tubal involvement, and parametrial involvement were independent risk factors. In subgroup analysis, univariate analysis showed that elevated CA-125 level and negative ER were associated with ovarian metastasis (P<0.05), however multivariate analysis revealed that only high CA-125 level was an independent risk factor (P<0.05). The incidence of ovarian metastasis in patients with high CA-125 level and who were ER-negative was 24%. For patients with normal CA-125 level and who were ER-positive, the incidence was 1.19%. The optimal cutoff value that provided the best sensitivity and specificity was 110.5 U/ml.ConclusionsThe incidence of ovarian metastasis in endometrial cancer is low. Ovarian preservation should be considered for women without abnormal CA-125 level and who have deeper myometrial invasion, tubal involvement, parametrial involvement, and who are ER-negative. These findings may facilitate clinical decision-making.

Whole-Volume Tumor MRI Radiomics for Prognostic Modeling in Endometrial Cancer.

BackgroundIn endometrial cancer (EC), preoperative pelvic MRI is recommended for local staging, while final tumor stage and grade are established by surgery and pathology. MRI‐based radiomic tumor profiling may aid in preoperative risk‐stratification and support clinical treatment decisions in EC.PurposeTo develop MRI‐based whole‐volume tumor radiomic signatures for prediction of aggressive EC disease.Study TypeRetrospective.PopulationA total of 138 women with histologically confirmed EC, divided into training (nT = 108) and validation cohorts (nV = 30).Field Strength/SequenceAxial oblique T1‐weighted gradient echo volumetric interpolated breath‐hold examination (VIBE) at 1.5T (71/138 patients) and DIXON VIBE at 3T (67/138 patients) at 2 minutes postcontrast injection.AssessmentPrimary tumors were manually segmented by two radiologists with 4 and 8 years' of experience. Radiomic tumor features were computed and used for prediction of surgicopathologically‐verified deep (≥50%) myometrial invasion (DMI), lymph node metastases (LNM), advanced stage (FIGO III + IV), nonendometrioid (NE) histology, and high‐grade endometrioid tumors (E3). Corresponding analyses were also conducted using radiomics extracted from the axial oblique image slice depicting the largest tumor area.Statistical TestsLogistic least absolute shrinkage and selection operator (LASSO) was applied for radiomic modeling in the training cohort. The diagnostic performances of the radiomic signatures were evaluated by area under the receiver operating characteristic curve in the training (AUCT) and validation (AUCV) cohorts. Progression‐free survival was assessed using the Kaplan–Meier and Cox proportional hazard model.ResultsThe whole‐tumor radiomic signatures yielded AUCT/AUCV of 0.84/0.76 for predicting DMI, 0.73/0.72 for LNM, 0.71/0.68 for FIGO III + IV, 0.68/0.74 for NE histology, and 0.79/0.63 for high‐grade (E3) tumor. Single‐slice radiomics yielded comparable AUCT but significantly lower AUCV for LNM and FIGO III + IV (both P < 0.05). Tumor volume yielded comparable AUCT to the whole‐tumor radiomic signatures for prediction of DMI, LNM, FIGO III + IV, and NE, but significantly lower AUCT for E3 tumors (P < 0.05). All of the whole‐tumor radiomic signatures significantly predicted poor progression‐free survival with hazard ratios of 4.6–9.8 (P < 0.05 for all).Data ConclusionMRI‐based whole‐tumor radiomic signatures yield medium‐to‐high diagnostic performance for predicting aggressive EC disease. The signatures may aid in preoperative risk assessment and hence guide personalized treatment strategies in EC.Level of Evidence4Technical Efficacy Stage2

PET Parameters are Useful in Predicting Endometrial Cancer Risk Classes and Prognosis.

We investigate the role of preoperative PET parameters to determine risk classes and prognosis of endometrial cancer (EC). We enrolled 81 patients with EC who underwent preoperative F-18 FDG PET/CT. PET parameters (SUVmax, SUVmean, MTV, TLG), grade, histology and size of the primary tumor, stage of the disease, the degree of myometrial invasion (MI), and the presence of lymphovascular invasion (LVI), cervical invasion (CI), distant metastasis (DM) and lymph node metastasis (LNM) were recorded. The relationship between PET parameters, clinicopathological risk factors and overall survival (OS) was evaluated. The present study included 81 patients with EC (mean age 60). Of the total sample, 21 patients were considered low risk (endometrioid histology, stage 1A, grade 1 or 2, tumor diameter < 4 cm, and LVI negative) and 60 were deemed high risk. All of the PET parameters were higher in the presence of a high-risk state, greater tumor size, deep MI, LVI and stage 1B-4B. MTV and TLG values were higher in the patients with non-endometrioid histology, CI, grade 3 and LNM. The optimum cut-off levels for differentiating between the high and low risk patients were: 11.1 for SUVmax (AUC = 0.757), 6 for SUVmean (AUC = 0.750), 6.6 for MTV(AUC = 0.838) and 56.2 for TLG(AUC = 0.835). MTV and TLG values were found as independent prognostic factors for OS, whereas SUVmax and SUVmean values were not predictive. The PET parameters are useful in noninvasively differentiating between risk groups of EC. Furthermore, volumetric PET parameters can be predictive for OS of EC.

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.