Endometrial Cancer Screening Research Articles

Interdisciplinary Diagnosis, Therapy and Follow-up of Patients with Endometrial Cancer. Guideline (S3-Level, AWMF Registry Nummer 032/034-OL, April 2018) - Part 1 with Recommendations on the Epidemiology, Screening, Diagnosis and Hereditary Factors of Endometrial Cancer.

Summary The first German interdisciplinary S3-guideline on the diagnosis, therapy and follow-up of patients with endometrial cancer was published in April 2018. Funded by German Cancer Aid as part of an Oncology Guidelines Program, the lead coordinators of the guideline were the German Society of Gynecology and Obstetrics (DGGG) and the Gynecological Oncology Working Group (AGO) of the German Cancer Society (DKG). Purpose The use of evidence-based, risk-adapted therapy to treat low-risk women with endometrial cancer avoids unnecessarily radical surgery and non-useful adjuvant radiotherapy and/or chemotherapy. This can significantly reduce therapy-induced morbidity and improve the patientʼs quality of life as well as avoiding unnecessary costs. For women with endometrial cancer and a high risk of recurrence, the guideline defines the optimal surgical radicality together with the appropriate chemotherapy and/or adjuvant radiotherapy where required. The evidence-based optimal use of different therapeutic modalities should improve survival rates and the quality of life of these patients. The S3-guideline on endometrial cancer is intended as a basis for certified gynecological cancer centers. The aim is that the quality indicators established in this guideline will be incorporated in the certification processes of these centers. Methods The guideline was compiled in accordance with the requirements for S3-level guidelines. This includes, in the first instance, the adaptation of source guidelines selected using the DELBI instrument for appraising guidelines. Other consulted sources include reviews of evidence which were compiled from literature selected during systematic searches of literature databases using the PICO scheme. In addition, an external biostatistics institute was commissioned to carry out a systematic search and assessment of the literature for one area of the guideline. The identified materials were used by the interdisciplinary working groups to develop suggestions for Recommendations and Statements, which were then modified during structured consensus conferences and/or additionally amended online using the DELPHI method with consent being reached online. The guideline report is freely available online. Recommendations Part 1 of this short version of the guideline presents recommendations on epidemiology, screening, diagnosis and hereditary factors, The epidemiology of endometrial cancer and the risk factors for developing endomentrial cancer are presented. The options for screening and the methods used to diagnose endometrial cancer including the pathology of the cancer are outlined. Recommendations are given for the prevention, diagnosis, and therapy of hereditary forms of endometrial cancer.

Modified capture-recapture estimates of the number of families with Lynch syndrome in Central Ohio.

Past methods for estimating the population frequency of familial cancer syndromes have used cases and controls ignoring the familial nature of genetic disease. In this study we modified the capture-recapture method from ecology to estimate the number of families in central Ohio with Lynch syndrome (LS). We screened 1566 colorectal cancer cases and 545 endometrial cancer cases in central Ohio from 1999 to 2005 and identified 58 with LS. We screened an additional 3346 colorectal and 342 endometrial cancer cases from 2013 to 2016 and identified 149 with LS. We found 12 LS mutations shared between families observed in the first and second studies. We identified three individuals between studies who were closely related and eight who were more distantly related. We used identified family relationships and genetic test results to estimate family size and structure. Applying a modified capture-recapture method we estimate 1693 3-generation families in the area who have 288 unique LS causing mutations. Comprehensive colorectal and endometrial cancer screening will take about 20years to identify 50% of families with LS. This is the first time that the capture-recapture method has been applied to estimate the burden of families with a specific heritable disease. Family structure reveals the potential extent of prevention and the time necessary to identify a proportion of families with LS.

Immunohistochemistry for mismatch repair protein deficiency in endometrioid endometrial carcinoma yields equivalent results when performed on endometrial biopsy/curettage or hysterectomy specimens

ObjectiveUniversal screening of endometrial cancer (EC) for Lynch syndrome (LS) has been increasingly implemented in the past five to ten years. Most pathologists initiate screening with immunohistochemistry (IHC) for mismatch repair proteins (MMRPs), using either pre-surgical samplings (endometrial biopsy or curettage, EMB/C) or hysterectomy specimens. We report a systematic assessment of the equivalence of IHC for LS screening on EMB/C versus hysterectomy specimens. MethodsWe identified 99 patients diagnosed with endometrioid EC and performed IHC for MMRPs MLH1, MSH2, MSH6, and PMS2 on their diagnostic EMB/C and paired hysterectomy specimen. Each specimen was scored as MMRP-retained or MMRP-deficient. ResultsNinety-one EMB/Cs had carcinoma, while 8 EMB/Cs showed only complex atypical hyperplasia (CAH). Carcinoma was identified in all 99 hysterectomy specimens. Considering all 99 patients tested, concordance of MMRP expression pattern between EMB/C and paired hysterectomy specimen was 100%. Sixty-nine cases retained all four MMRPs, while 30 were MMRP deficient (26 MLH1- and PMS2-deficient, 3 MSH2- and MSH6-deficient, 1 PMS2-deficient). ConclusionsIn screening for LS in EC, IHC for MMRPs can be performed with identical accuracy on either EMB/C or hysterectomy specimens. Routine testing of diagnostic EMB/Cs may lead to earlier detection of MMRP deficiency, with improved patient uptake of genetic counseling and potential for earlier identification of immunotherapy candidates. Furthermore, reliable IHC-based LS screening performed on EMB/C can guide patient management and genetic counseling in patients unable to undergo hysterectomy.

Risk of high-grade lesions after atypical glandular cells in cervical screening: a population-based cohort study

ObjectivesTo determine how human papillomavirus (HPV) positivity of atypical glandular cells (AGCs) affects the predictive values for the presence of high-grade cervical lesions.DesignPopulation-based cohort study.SettingStockholm-Gotland region, Sweden.ParticipantsBetween 17 February 2014...

Analysis on the value of cytological and histological noninvasive methods in endometrial cancer screening

Objective To explore the value of cytological and histological noninvasive methods in the screening of endometrial cancer (EC). Methods Seventy-six cases of suspected EC high risk patients diagnosed in the gynecological outpatient department of the People Hospital of Longhua from January 2015 to May 2017 were selected as the research object, the endometrial cells and tissues were collected for cytological and histological examination, the diagnosis of curettage or hysteroscopy performed as agold standardto determine the effect of cytology, histology and combined examination on the ensitivity, specificity, positive coincidence rate of EC diagnosis. Results 76 patients with suspected EC high risk factors were diagnosed as EC 48 cases (63.16%) viagold standard. The sensitivity, specificity and positive coincidence rate of cytology were (75.00%, 89.29%, 80.26%, χ2=1.0105, P=0.6033), histology were(79.17%, 92.86%, 84.21%, χ2=0.3117, P=0.8557) and combined examination in EC were(83.33%, 92.86%, 86.84%, χ2=1.2260, P=0.5417). Conclusion Cytological and histological noninvasive screening has high sensitivity, specificity and positive coincidence rate in EC and has a high diagnostic value for individual or combined exams and can be used as a routine screening for EC in clinical practice. Key words: Endometrial Cancer; Cytology; Histology

Universal screening for Lynch syndrome in endometrial cancers: frequency of germline mutations and identification of patients with Lynch-like syndrome

Lynch syndrome (LS) is an inherited clinical syndrome characterized by a high risk of colorectal, endometrial (lifetime risk of up to 60%), ovarian, and urinary tract cancers. The diagnosis is confirmed by identification of germline mutations in the DNA mismatch repair genes MLH1, PMS2, MSH2, MSH6, or EPCAM. In 2015, our institution implemented universal screening of endometrial cancer (EC) hysterectomy specimens by mismatch repair immunohistochemistry (IHC) with reflex MLH1 promoter hypermethylation analysis for tumors with loss of MLH1/PMS2 expression. Patients with tumors negative for MLH1 methylation and those with a loss of the heterodimer pair MSH2 and MSH6, or isolated loss of either PMS2 or MSH6 were referred to the Familial Cancer Program for genetic counseling and consideration of germline testing. Between May 2015 to Dec 2016, 233 EC patients were screened by IHC for LS with a median age of 63 years. Sixty tumors (27%) had abnormal IHC staining results. Fifty-one (22%) harbored heterodimeric loss of MLH1 and PMS2, 49 of which showed MLH1 promoter methylation (1 failure, 1 negative). One showed loss of MLH1/PMS2 and MSH6, 2 showed loss of MSH2/MSH6, and 6 had isolated loss of MSH6 only. Ten patients underwent genetic counseling, and germline testing was performed in 8; LS was confirmed in 5 patients (2.1%). In addition, 3 patients with negative germline testing and presumed Lynch-like syndrome were identified and offered additional somatic testing. Universal screening for LS in EC patients has yielded positive results for identification of patients at risk for this inherited syndrome.

Clinical characteristics of Lynch-like cases collaterally classified by Lynch syndrome identification strategy using universal screening in endometrial cancer.

Lynch syndrome (LS), an autosomal-dominant inherited disorder, increases the risk for LS-associated cancers (LS-AC). Molecular LS assessment for all cases is referred to as universal screening (U/S) and is recommended for endometrial cancer (EC) and colorectal cancer. Lynch-like cases (LL) lack LS-pathogenic mutations despite being suspected as LS by U/S, but have been poorly investigated in EC. The aim of this study was to capture the features of LL in EC and to devise LL management in EC. U/S, consisting of immunohistochemistry and reflex methylation analysis, was applied to 348 Asian ECs, and sporadic cancer (SC) cases were screened out. Genetic testing was offered to "suspected-LS" cases selected by U/S. The features of the LS, LL, and SC groups were recorded and compared. U/S screened 306 ECs as SC. The recurrence rates of suspected-LS and SC cases were 14.3% (6/42) and 26.5% (81/306), respectively. Of the 42 suspected-LS cases, 10 were identified as LS, 17 were classified as LL, and 15 did not undergo genetic testing. In the LS group, the frequency of personal history (50%) and family history (100%) of LS-AC were prominent. Of note, the prevalence of family history of LS-AC and gastric cancer was significantly higher in the LL group than in the SC group (76.5% vs. 38.6% and 47.1% vs. 25.2%, respectively). Herein, we report the features of LL classified by LS identification via U/S in Asian EC. LL should be candidates for tailored surveillance based on regionality and family history.

Current strategies in the diagnosis of endometrial cancer.

Endometrial cancer is the most common gynecological malignancy in developed countries. There are no uniform recommendations for endometrial cancer screening in the general population. Therefore, it is of paramount importance that the primary physician profoundly understands, and is familiar with the methods for prevention and early detection of endometrial cancer. The aim of this review is to provide the primary physician with a toolbox to reach these goals. We performed a systemic review to summarize the current strategies to diagnose and prevent endometrial cancer. Many published articles from the last years were identified and included. A systematic review that summarizes the important subjects in the diagnosis and prevention of endometrial cancer. Maintaining a high index of suspicion and obtaining endometrial biopsies from all suspected patients is the key for achieving a timely diagnosis.

Clinical application value of endometrial collector combined with liquid based cytology and histological examination for screening of endometrial cancer

Objective To analyze the clinical application value of endometrial collector combined with liquid based cytology and histological examination for screening of endometrial cancer. Methods One hundred and eighty-two cases high-risk people with endometrial cancer in Songgang People's Hospital of Bao'an district of Shenzhen from June 2014 to December 2015 were collected, among them 71 patients with endometrial cancer were found in the patients who were diagnosed by pathological diagnosis, and the remaining 111 were not diagnosed with endometrial cancer.The material satisfaction, sample collection time of sample collection and endometrial curettage device were comparatively analyzed and also the cervical dilatation production rate, the amount of bleeding, pain score(VAS) were analyzed.The application value of endometrial collector combined with liquid based cytology and histological examination for screening of endometrial cancer was judged according to the results obtained. Results There was no significant difference between the two methods based on satisfaction(χ2=1.953, P=0.089). A methods of cervical endometrial expansion rate(3.85% vs.93.96%) and acquisition time((16.35±2.19) min vs.(11.23±4.26) min), bleeding volume((1.64±0.63) ml vs.(15.73±5.41) ml), VAS score((0.82±0.24) points vs.(4.34±2.43) points) were significantly lower than that of curettage sample collection method(χ2=16.473, P=0.000; t=5.733, P=0.034; t=11.183, P=0.000; t=3.618, P=0.043). With curettage pathological diagnosis as the gold standard, the specificity, sensitivity and diagnostic coincidence rate of endometrial biopsy combined with liquid based cytology and histological examination for screening endometrial carcinoma were respectively 94.51%, 95.05% and 94.96%. Conclusion Compared with curettage sampling method, endometrial curettage collector has features of high success rate, short time, low pain and high security and the cervical dilation rate is low.Endometrial curettage collector can be combined with liquid based cytology and histology to examine and screen endometrial cancer.This methods is worth promoting. Key words: Endometrial collector; Liquid based cytology; Histology; Endometrial carcinoma; Clinical value

Integrated Epigenomics Analysis Reveals a DNA Methylation Panel for Endometrial Cancer Detection Using Cervical Scrapings.

Endometrial cancer is a common gynecologic cancer whose incidence is increasing annually worldwide. Current methods to detect endometrial cancer are unreliable and biomarkers are unsatisfactory for screening. Cervical scrapings were reported as a potential source of material for molecular testing. DNA methylation is a promising cancer biomarker, but limited use for detecting endometrial cancer. We analyzed two methylomics databases of endometrioid-type endometrial cancer. Using nonnegative matrix factorization algorithm clustered the methylation pattern and reduced the candidate genes. We verified in pools DNA from endometrial cancer tissues and cervical scrapings, and validated in 146 cervical scrapings from patients with endometrioid-type endometrial cancer (n = 50), uterine myoma (n = 40), and healthy controls (n = 56) using quantitative methylation-specific PCR (QMSP). The logistic regression was used to evaluate the performance of methylation signal and gene combination. We filtered out 180 methylated genes, which constituted four consensus clusters. Serial testing of tissues and cervical scrapings detected 14 genes that are hypermethylated in endometrial cancer. Three genes, BHLHE22, CDO1, and CELF4, had the best performance. Individual genes were sensitivity of 83.7%-96.0% and specificity of 78.7%-96.0%. A panel comprising any two of the three hypermethylated genes reached a sensitivity of 91.8%, specificity of 95.5%, and odds ratio of 236.3 (95% confidence interval, 56.4-989.6). These markers were also applied to cervical scrapings of type II endometrial cancer patients, and detected in 13 of 14 patients. This study demonstrates the potential use of methylated BHLHE22/CDO1/CELF4 panel for endometrial cancer screening of cervical scrapings. Clin Cancer Res; 23(1); 263-72. ©2016 AACR.

The diagnostic value of tumor abnormal protein and high sensitivity C reactive protein in screening for endometrial cancer with endometrial thickness less than 8 mm ⁎

Abstract Objective This study aimed to combine tumor abnormal protein (TAP) and high-sensitivity C-reactive protein (hs-CRP) level detection to diagnose endometrial cancer in patients with endometrial thickness less than 8 mm, and to provide a reference for clinical screening and diagnosis. Methods Clinical data from 19 cases of endometrial cancer, diagnosed on the basis of pathological findings, were collected from September 2014 to December 2015. The inclusion criteria were as follows: the patients were first diagnosed with endometrial thickness less than 8 mm and were all in menopause. Perimenopausal patients (n = 26) with uterine fibroids seen during the same period were selected as a control group. Serum TAP and hs-CRP levels of the patients in the two groups were simultaneously determined on admission. Results We found that both TAP and hs-CRP levels in the experimental group were higher than those in the control group [(182.95 ± 72.14) μm2 vs. (133.19 ± 55.18) μm2, P = 0.019; (7.52 ± 19.03) mg/L vs. (1.66 ± 2.31) mg/L, P = 0.136]. The sensitivity of TAP for the diagnosis of endometrial cancer was 73.68%, the specificity was 69.23%, and the Youden index was 0.4291. The diagnostic sensitivity and specificity of hs-CRP was 15.79% and 100%, respectively, and the Youden index was 0.1579. After plotting the receiver operating characteristics curves, the optimal cut-off value for TAP in diagnosing endometrial cancer was found to be 160.662 μm2 and that for hs-CRP was 1.07 mg/L. Conclusion For patients suspected of having endometrial cancer with endometrial thickness less than 8 mm, combined detection of TAP and hs-CRP levels can be used as a screening tool and can provide new ideas regarding clinical diagnosis and treatment.

Role of Liquid-based Cytology and Cell Block in the Diagnosis of Endometrial Lesions.

Background:Liquid-based cytology (LBC) offers an alternative method to biopsy in screening endometrial cancer. Cell block (CB), prepared by collecting residual cytological specimen, represents a novel method to supplement the diagnosis of endometrial cytology. This study aimed to compare the specimen adequacy and diagnostic accuracy of LBC and CB in the diagnosis of endometrial lesions.Methods:A total of 198 women with high risks of endometrial carcinoma (EC) from May 2014 to April 2015 were enrolled in this study. The cytological specimens were collected by the endometrial sampler (SAP-1) followed by histopathologic evaluation of dilatation and curettage or biopsy guided by hysteroscopy. The residual cytological specimens were processed into paraffin-embedded CB after LBC preparation. Diagnostic accuracies of LBC and CB for detecting endometrial lesions were correlated with histological diagnoses. Chi-square test was used to compare the specimen adequacies of LBC and CB.Results:The specimen inadequate rate of CB was significantly higher than that of LBC (22.2% versus 7.1%, P < 0.01). There were 144 cases with adequate specimens for LBC and CB preparation. Among them, 29 cases were atypical endometrial hyperplasia (11 cases) or carcinoma (18 cases) confirmed by histology evaluation. Taking atypical hyperplasia and carcinoma as positive, the diagnostic accuracy of CB was 95.1% while it was 93.8% in LBC. When combined LBC with CB, the diagnostic accuracy was improved to 95.8%, with a sensitivity of 89.7% and specificity of 97.4%.Conclusions:CB is a feasible and reproducible adjuvant method for screening endometrial lesions. A combination of CB and LBC can improve the diagnostic accuracy of endometrial lesions.

National genetic screening for endometrial cancer

Endometrial cancer is the most common gynecologic malignancy in developed countries, with an average incidence of 14.7/100,000 women and ranks second place after cervical cancer in developing countries, with an average incidence of 5.5/100,000. The global average incidence in 2012 was 8.2/100,000 women, representing 319 605 cases of cancer of the endometrium. The reported incidence in 2012 of cancer of the endometrium for Romania was 8.46/100000 women, within Europe the same year average was 13.6/100,000 women. In Romania, pick the incidence occurs in the age group 60-64 years (42.8/100,000 women), the cumulative risk being 1%. According to World Health Organization predictive estimates for Romania is expected for 2015 an increase in the number of new cases by 2.92% to 10.07% for 2025 and for 2035 with 15.33%, of whom, under the age of 65 years in 2015 will be 990 new cases, in 2025 will be 986 new cases and in 2035 under this age will be 1027 new cases of cancer of the endometrium. The data for the period 2005-2015 was investigated coming from reports of family doctors, the national registry for cancer and (SIUI). Of the total of admissions for diagnosed endometrial cancer, 10% have affected women under 50 years, and 2.78% women under 40 years. Studying the National Registry for Cancer for 2005-2007, regarding new cases reported by district oncology cabinets, an average number of 108 new endometrial cancer cases/year has resulted and respectively 237 new colorectal cancer cases for women under 50. The total number is significant, representing the patients whose genetic testing is essential for defining an important high risk group for familial cancer, a fact that is universally accepted, the screening which is intended for.

Assessment of Cervicovaginal Cancer Antigen 125 Levels: A Preliminary Study for Endometrial Cancer Screening

Aim: We primarily aimed to compare the levels of serum and cervicovaginal cancer antigen 125 (CA 125) in women with and without endometrial carcinoma in order to reveal whether cervicovaginal CA 125 could be used as a non-invasive method. Methods: A preliminary case-control study was designed. The study group consisted of patients who were operated for endometrial adenocarcinoma or endometrial intraepithelial neoplasia. The control group consisted of patients who underwent surgery for benign gynecological diseases. Serum and cervicovaginal secretions were immediately collected before surgery to compare levels of CA 125. Results: The mean cervicovaginal CA 125 levels in patients with endometrial cancer and controls were 1,598.1 ± 1,691.1 versus 947.0 ± 1,282.7 U/ml, respectively (p = 0.016). Whereas area under receiver operating characteristic curve was 0.62 for serum CA 125, it was 0.68 for cervicovaginal CA 125. The optimal threshold of CA 125 in cervicovaginal secretion was calculated to be 575 U/ml, which detected endometrial precancer or cancer with sensitivity of 78% and specificity of 57%. The positive and negative predictive values for this threshold were 38.7 and 88.2%, respectively. Conclusion: In conclusion, detection of CA 125 in cervicovaginal secretion has a potential role for the non-invasive screening of endometrial precancers and cancers.

Screening and diagnosis of endometrial cancer in Lynch syndrome

Screening and diagnosis of endometrial cancer in Lynch syndrome

Endometrial evaluation with transvaginal ultrasonography for the screening of endometrial hyperplasia or cancer in premenopausal and perimenopausal women.

ObjectiveThe aim of our study is to determine clinical factors and sonographic findings associated with endometrial hyperplasia or cancer (EH+) in premenopausal and perimenopausal women.MethodsA total of 14,340 transvaginal ultrasonography examinations of 9,888 healthy premenopausal and perimenopausal women were included in this retrospective study. One hundred sixty-two subjects underwent endometrial biopsy based on abnormal uterine bleeding (AUB), sonographic endometrial abnormalities (thickened endometrium, endometrial mass, or endometrial stripe abnormality), or both. The clinical factors and sonographic endometrial abnormalities were evaluated with regard to EH+.ResultsHistologically verified EH+ was found in fourteen subjects (8.6%); ten cases of endometrial hyperplasia (EH) without atypia, three cases of EH with atypia (AEH), and one case of endometrial cancer. Neither clinical factors nor AUB were associated with EH+ (P=0.32) or AEH+ (P=0.72). Of sonographic findings, endometrial stripe abnormality was significantly associated with EH+ (P=0.003) and marginally associated with AEH+ (P=0.05), but a thickened endometrium was not associated with EH+ (P=0.43).ConclusionEndometrial stripe abnormality is a significant factor to predict EH+ in healthy premenopausal and perimenopausal women with and without AUB. However, simple measurement of endometrial thickness has a limited role in this capacity.

Cancer of the corpus uteri.

Cancer of the corpus uteri.

Advance of endometrial cancer screening

Endometrial cancer is one of the common malignant tumors in female genital tract. The incidence of endometrial cancer is increasing, even the top one in the developed country and bigger cities in China. The screening of endometrial cancer should be performed in the high risk population. In the recent years, the popular screening methods for endometrial cancer include ultrasound, endometrial biopsy, and endometrial cytology (ECT), etc. This review introduces briefly above methods. Key words: Endometrial neoplasms/DI; Review

Prospective performance study of the liquid based endometrial cytology not inferior to suction endometrial tissue biopsy for the endometrial cancer screening.

e16523 Background: Since the need of the early detection and treatment of endometrial cancer continues increasing in Japan, the development of the reliable and easy practical method to detect the e...

A Prospective Study on the Application of Endometrial Cytology Examination in the Screening of Endometrial Cancer

Background: Endometrial cancer is one of the most common gynecology malignancies. But there is still lack of an accurate, reliable, convenient, easy, economical and practical method for early detection of endometrial cancer and precancerous lesions. The aim of this study is to evaluate the specimen quality and diagnostic accuracy of endometrial cytology examination in the screening of endometrial cancer. Methods: 95 patients with abnormal uterine bleeding or vaginal ultrasound examination results indicating intrauterine abnormalities and needing endometrial examination were investigated, and specimens were collected using endometrial sampling device for cytology (ESDC) and sliced using thinprep cytology test (TCT), meanwhile, hysteroscopy auxiliary diagnostic curettage and histopathological examination were performed. Results: The satisfaction rate was 100% for the specimens collected using ESDC and 97.9% for those using diagnostic curettage. The difference in the satisfaction rate of collecting specimens was statistically significant between the two methods, and the satisfaction rate of collecting specimen using endometrial cytology was superior to that using diagnostic curettage. Taking diagnostic curettage histopathologic results as "gold standard", the sensitivity of endometrial cytology was 63.6%, specificity 93.6%, positive predictive value 70% and negative predictive value 95.2% in the screening of endometrial cancer. Conclusion: Endometrial cytology can be used as a reliable, safe and simple method in the screening of endometrial cancer.