Endometrial Cancer Screening Research Articles

Lynch syndrome screening in endometrial cancer patients with immunohistochemistry: A single center experience

Objectives: Universal screening for Lynch syndrome (LS) using immunohistochemistry (IHC) is recommended for patients with new colon cancer. While the sentinel malignancy in women with Lynch syndrome is equally as likely to be endometrial cancer compared to colon cancer, universal screening in endometrial cancer has not been implemented on such a large scale. Our study aims to determine any associations between loss of MMR expression and tumor clinico-pathologic characteristics, as well as the number of germ line mutations identified using IHC at our institution.

The endoglin–BMP9 axis as a predictor of methotrexate resistance in low-risk gestational trophoblastic neoplasia

Objectives: Universal screening for Lynch syndrome (LS) using immunohistochemistry (IHC) is recommended for patients with new colon cancer. While the sentinel malignancy in women with Lynch syndrome is equally as likely to be endometrial cancer compared to colon cancer, universal screening in endometrial cancer has not been implemented on such a large scale. Our study aims to determine any associations between loss of MMR expression and tumor clinico-pathologic characteristics, as well as the number of germ line mutations identified using IHC at our institution. Methods: A retrospective review of patients who underwent hysterectomy for grade 1 or 2 endometrioid endometrial cancer between August 2012 and January 2014 was performed. Only patients who underwent IHC for deficiencies of MLH1, MSH2, MSH6, and PMS2 were included in this cohort. Patient charts were reviewed and patient demographics, tumor size, grade, invasion, and stainingwere abstracted from electronic medical records. Results: 180 patients underwent hysterectomy for low grade EEC during the study period. Of these, 102 (56.6%) had IHC to evaluate for MMR protein deficiencies. Twenty six (25.5%) tumors had MMR loss detected via IHC, with 19 (18.6%) having deficiencies in MLH1/ PMS2 and 3 (2.9%) in MSH2/MSH6. Loss of single protein expression was observed in 4 patients, with loss of MSH6 expression noted in 2 (2.0%) and loss of MLH1 and PMS2 in 1 (1%) each. MLH1 promoter methylation analysis was performed in 7 (35.0%) of the 20 tumors, showing methylation in 6 (85.7%). One patient with MSH2 and MSH6 loss by IHC was found to have a germline mutation in MSH6. Grade 2 tumors were significantly associated with MLH1 loss on multivariate analysis (OR 5.3, p = 0.012, 95% CI 1.4–19.8). Increasing age was associated with MLH1 and PMS2 loss (OR 1.2, p = 0.021, 95% CI 1.0– 1.3). Younger age was significantly associated with MSH6 loss (OR 0.79, p = 0.025, 95% CI .64–.97). Conclusions: The most common deficiency detected via IHC involves MLH1 and PMS2 loss and is significantly associated with age. Loss of MSH6 is significantly associated with younger age. Large studies with cost-effectiveness analyses must be performed to determine if implementation of a standardized screening regimen is necessary.

The impact of chemotherapy on survival in uterine clear cell carcinoma patients

Objectives: Universal screening for Lynch syndrome (LS) using immunohistochemistry (IHC) is recommended for patients with new colon cancer. While the sentinel malignancy in women with Lynch syndrome is equally as likely to be endometrial cancer compared to colon cancer, universal screening in endometrial cancer has not been implemented on such a large scale. Our study aims to determine any associations between loss of MMR expression and tumor clinico-pathologic characteristics, as well as the number of germ line mutations identified using IHC at our institution. Methods: A retrospective review of patients who underwent hysterectomy for grade 1 or 2 endometrioid endometrial cancer between August 2012 and January 2014 was performed. Only patients who underwent IHC for deficiencies of MLH1, MSH2, MSH6, and PMS2 were included in this cohort. Patient charts were reviewed and patient demographics, tumor size, grade, invasion, and stainingwere abstracted from electronic medical records. Results: 180 patients underwent hysterectomy for low grade EEC during the study period. Of these, 102 (56.6%) had IHC to evaluate for MMR protein deficiencies. Twenty six (25.5%) tumors had MMR loss detected via IHC, with 19 (18.6%) having deficiencies in MLH1/ PMS2 and 3 (2.9%) in MSH2/MSH6. Loss of single protein expression was observed in 4 patients, with loss of MSH6 expression noted in 2 (2.0%) and loss of MLH1 and PMS2 in 1 (1%) each. MLH1 promoter methylation analysis was performed in 7 (35.0%) of the 20 tumors, showing methylation in 6 (85.7%). One patient with MSH2 and MSH6 loss by IHC was found to have a germline mutation in MSH6. Grade 2 tumors were significantly associated with MLH1 loss on multivariate analysis (OR 5.3, p = 0.012, 95% CI 1.4–19.8). Increasing age was associated with MLH1 and PMS2 loss (OR 1.2, p = 0.021, 95% CI 1.0– 1.3). Younger age was significantly associated with MSH6 loss (OR 0.79, p = 0.025, 95% CI .64–.97). Conclusions: The most common deficiency detected via IHC involves MLH1 and PMS2 loss and is significantly associated with age. Loss of MSH6 is significantly associated with younger age. Large studies with cost-effectiveness analyses must be performed to determine if implementation of a standardized screening regimen is necessary.

Combined colonoscopy and endometrial biopsy cancer screening results in women with Lynch syndrome

ObjectiveEndometrial biopsy (EMBx) and colonoscopy performed under the same sedation is termed combined screening and has been shown to be feasible and to provide a less painful and more satisfactory experience for women with Lynch syndrome (LS). However, clinical results of these screening efforts have not been reported. The purpose of this study was to evaluate the long-term clinical outcomes and patient compliance with serial screenings over the last 10.5years. MethodsWe retrospectively analyzed the data for 55 women with LS who underwent combined screening every 1–2years between 2002 and 2013. Colonoscopy and endometrial biopsy were performed by a gastroenterologist and a gynecologist, with the patient under conscious sedation. ResultsOut of 111 screening visits in these 55 patients, endometrial biopsies detected one simple hyperplasia, three complex hyperplasia, and one endometrioid adenocarcinoma (FIGO Stage 1A). Seventy-one colorectal polyps were removed in 29 patients, of which 29 were tubular adenomas. EMBx in our study detected endometrial cancer in 0.9% (1/111) of surveillance visits, and premalignant hyperplasia in 3.6% (4/111) of screening visits. No interval endometrial or colorectal cancers were detected. ConclusionsCombined screening under sedation is feasible and less painful than EMBx alone. Our endometrial pathology detection rates were comparable to yearly screening studies. Our results indicate that screening of asymptomatic LS women with EMBx every 1–2years, rather than annually, is effective in the early detection of (pre)cancerous lesions, leading to their prompt definitive management, and potential reduction in endometrial cancer.

Should the Annual Pelvic Examination Go the Way of Annual Cervical Cytology?

The value of pelvic examination for healthy asymptomatic women has been called into question given the lack of benefit for ovarian and endometrial cancer screening, the ability to screen for sexually transmitted infections without a pelvic examination, and the uncoupling of the procurement of contraception with a pelvic examination. Still, there are indications for performing pelvic examinations in symptomatic women and in some high risk women. How do we as clinicians apply current evidence and expert opinion to our medical practice? Our recommendation to consider a pelvic examination at 3-5-year intervals with cervical cancer screening to elicit gynecologic and sexual health concerns offers a compromise between continuation of unnecessary annual pelvic examinations and complete elimination of these examinations.

Consequences of universal MSI/IHC in screening ENDOMETRIAL cancer patients for lynch syndrome

ObjectiveDetermine factors impacting the uptake of genetic counseling and results of genetic testing following universal tumor testing for Lynch syndrome in patients with endometrial cancer. MethodsThe study population consisted of two unselected cohorts of endometrial cancer patients, 408 identified retrospectively and 206 identified prospectively. Immunohistochemistry for mismatch repair protein expression and/or microsatellite instability analysis was performed on these tumors. MLH1 methylation analysis was performed on tumors with loss of MLH1 protein. Tumor studies were considered suggestive of Lynch Syndrome if they showed immunohistochemical loss of MSH2, MSH6 or PMS2, loss of MLH1 without MLH1 promoter methylation, and/or microsatellite instability. Participants with suggestive tumor studies were contacted and offered genetic counseling and testing. ResultsIn the retrospective cohort, 11% had tumor studies suggestive of Lynch syndrome, and 42% was seen for genetic counseling. A germline mutation was detected in 40%, and one had a variant of uncertain significance. In the prospective cohort, 8.7% of patients had tumor testing suggestive of Lynch syndrome; 72% were seen for genetic counseling. Germline mutations were found in 40%, and one had a variant of uncertain significance. Common challenges included timing of re-contact, age, perceived lack of relevance, inability to travel and limited insurance coverage. ConclusionsThere are several barriers to genetic counseling and testing follow-up after universal tumor testing, and uninformative genetic test results present a management challenge. It is important to consider these limitations when implementing an approach to screening endometrial cancer patients for Lynch syndrome.

Effective endometrial cancer screening method using liquid-based cytology

Effective endometrial cancer screening method using liquid-based cytology

Association of Tumor Morphology With Mismatch-repair Protein Status in Older Endometrial Cancer Patients

Although there is consensus on the cost-effectiveness of a universal approach of screening all colorectal cancer patients for Lynch syndrome (LS) using mismatch-repair (MMR) protein immunohistochemistry (IHC) and/or microsatellite instability (MSI) testing, the question of universal versus selective screening of endometrial cancer patients remains to be resolved. We have prospectively implemented a selective screening algorithm for newly diagnosed endometrial cancer patients, triggered by patient age 50 years or younger, personal/family cancer pedigree that meets Bethesda guideline criteria, and/or presence of MMR-associated tumor morphology. Four-protein MMR IHC and MSI testing were performed if any of the criteria were met. This algorithm excluded screening of older patients without a cancer pedigree and whose tumors lacked MMR morphology. The aim of this study was to retrospectively determine whether these exclusion criteria missed any tumors with abnormal MMR. Among 273 consecutive patients with newly diagnosed endometrial cancers, 181 (66%) lacked criteria for screening. Retrospective MMR IHC confirmed intact MMR in 177 (97.8%) of these 181 unscreened patients, loss of MSH6 in 1 patient (0.5%), and loss of MSH1/PMS2 due to MLH1 promoter hypermethylation in 3 patients (1.7%). In comparison, 41% of patients fulfilling 1 or more criteria for screening had abnormal MMR IHC/MSI, mostly consisting of loss of MLH1/PMS2. MMR morphology contributed to detection of 92% of the abnormal MMR cases while cancer pedigree contributed to detection of the remainder. All of the abnormalities due to MSH2 and PMS2 were detected by the screening algorithm, but 1 of the 4 MSH6 cases was not. The latter finding is consistent with the literature that MSH6 endometrial cancers exhibit a phenotype different than those of the other MMR genes. We conclude that a genotype-specific approach to screening endometrial cancer for LS could consist of universal testing by MSH6 IHC and selective testing by MLH1, PMS2, and MSH2 IHC on the basis of age, cancer pedigree, and MMR morphology. Cost-effectiveness of this hybrid selective strategy deserves further study, particularly in comparison with a universal strategy. Further work to identify phenotypic features of endometrial cancers with methylated MLH1 that would allow them to be excluded from LS screening would also contribute to cost-effectiveness.

Prospective performance study of the liquid-based endometrial cytology with sampling directly from the uterine endometrium for the effective endometrial cancer screening.

e16548 Background: In Japan, endometrial cytology by intrauterine sampling is one of the most common tests for evaluating the status of the endometrium. This method is usually applied as the initia...

Knowledge of Lynch syndrome among obstetrician/gynecologists and general surgeons

ObjectiveTo determine comfort and knowledge among obstetrician/gynecologists and general surgeons regarding recommendations for cancer screening for women with Lynch syndrome. MethodsA questionnaire on Lynch syndrome was administered to all obstetrician/gynecologists and general surgeons at a hospital in New York, USA. ResultsFifty obstetrician/gynecologists and 62 general surgeons completed the survey (67% response rate). Physicians were more comfortable counseling on colon cancer than endometrial cancer screening (51% vs 28%; P<0.001). Obstetrician/gynecologists were more comfortable than general surgeons counseling patients on endometrial cancer screening (36% vs 21%; P=0.090) but less comfortable counseling patients on colon cancer screening (36% vs 63%; P=0.008). There was no significant difference between the specialties in the number of knowledge-based questions answered correctly. Furthermore, there was no correlation between a physician’s perceived knowledge and number of correct answers. ConclusionMost physicians did not report being comfortable counseling about recommendations for endometrial cancer screening. While obstetrician/gynecologists reported greater comfort than general surgeons, we found no significant difference in disease knowledge between the groups. Because appropriate cancer screening can improve the outcomes of patients with Lynch syndrome, physicians must be knowledgeable and comfortable with screening recommendations for both endometrial and colon cancer, regardless of clinical specialty.

Case of uterine papillary serous carcinoma following tamoxifen treatment that could not be diagnosed during screening

This case involved a 69-year-old woman who had been taking tamoxifen for 5 years after breast cancer surgery. She was referred to our clinic for endometrial cancer screening when tamoxifen was first prescribed. Subsequently, transvaginal ultrasonography and endometrial cytology were performed every 6 months. Despite these regular examinations, stage IVb papillary serous carcinoma was detected 8 months after the end of tamoxifen administration. Total abdominal hysterectomy was performed, but only a small polyp was seen upon macroscopic examination of the uterus. However, papillary serous carcinoma was found microscopically in almost all lymphovascular spaces in the uterus from the endometrium to the serosa. On the surface of the polyp, only endometrial intraepithelial carcinoma with positive immunostaining for p53 was detected. Chemotherapy, including a platinum compound, was administrated, but unfortunately it was ineffective and the patient died of her disease 14 months after the operation.

Evaluation of Endometrial Precancerous Lesions in Postmenopausal Obese Women - A High Risk Group?

To evaluate precancerous lesions such as hyperplasia and endometrial polyps in obese postmenopausal women. Women who were referred with abnormal uterine bleeding in postmenopausal period or the presence of endometrial cells on cervical cytology in our department were investigated. Anthropometric measurements such as height, weight, body mass index, waist/hip ratio and endometrial thickness were compared between a precancerous lesion (hyperplasia and endometrial polyp) group and a pathologically normal group. We detected statistically significant thickening of endometrium in patients with precancerous lesions. Moreover patients with precancerous lesions had higher body mass index than the pathologically normal group. We found elevated precancerous lesion rates in overweight and obese women in the postmenopausal period, of interest given that the prevalence of obesity is increasing in most parts of the world. Although screening for endometrial cancer is not recommended for the general population, in high-risk populations like obese postmenopausal women, it may be very important.

Preinvasive Lesions in Gynaecology – Endometrium

Preinvasive lesions of the endometrium are histopathological and molecular alterations related to high-risk of uterine carcinoma development. Incidence has increasing tendency. Atypical endometrial hyperplasia is the preinvasive lesion of type I endometrial carcinoma, developing under a hyperestrogenic background. Carcinoma in situ of the endometrium is considered to be precursor lesion of type II endometrial carcinoma, first of all uterine serous carcinoma. Hysterectomy and bilateral oophorectomy is the main therapeutical modality in both preinvasive lesions of the endometrium. The hormonal therapy with progestogens is the possibility of fertility sparing approach in treatment of histological findings of atypical endometrial hyperplasia in young women. Even though preinvasive lesions of the endometrium are clearly defined, the possibilities of endometrial cancer screening are markedly limited.

Outcomes of screening endometrial cancer patients for Lynch syndrome by patient-administered checklist

ObjectiveThe aims of this study were to implement a patient-administered checklist designed to identify endometrial cancer patients at elevated risk for Lynch syndrome; measure subsequent genetic counseling and testing; and identify differences between those who attended genetic counseling and those who did not. MethodsWe developed a 4-item yes/no checklist of personal and family history risk factors for Lynch syndrome-associated endometrial cancer and recommended referral for genetic counseling for patients meeting any of the criteria. Retrospective chart review was performed to determine subsequent genetic counseling and testing outcomes over a 15month period. Results6/387 (1.6%) of endometrial cancer patients tested positive for a Lynch syndrome mutation. 4/24 (17%) of endometrial cancer patients who met referral criteria and attended genetic counseling tested positive. 38/70 (55%) of patients who met referral criteria were not seen for genetic counseling. Patients who were diagnosed with endometrial cancer at younger ages, who had primary surgery at our institution, or who met more than one referral criteria were more likely to be seen for genetic counseling. ConclusionsEndometrial cancer patients who met referral criteria and attended genetic counseling comprised a population enriched for Lynch syndrome. This approach allowed Lynch syndrome evaluation resources to be targeted to a population of patients that is high risk and interested in the information. The referral rate of at-risk patients needs to be improved, and allocating resources towards this goal could increase the identification of Lynch syndrome while avoiding some of the pitfalls of universal screening.

Familial risk-colorectal cancer: ESMO Clinical Practice Guidelines

J. Balmana1, F. Balaguer2, A. Cervantes3 & D. Arnold4, on behalf of the ESMO Guidelines Working Group* Department of Medical Oncology, Hospital Vall d’Hebron, Vall d’Hebron Institute of Oncology (VHIO), Universitat Autonoma de Barcelona, Barcelona; Department of Gastroenterology, Hospital Clinic, CIBERehd, IDIBAPS, University of Barcelona, Barcelona; Department of Hematology and Medical Oncology, INCLIVA, University of Valencia, Valencia, Spain; Department of Medical Oncology, Tumor Biology Clinic, Albert Ludwigs University, Freiburg, Germany;

Early detection of ovarian and fallopian tube cancer by examination of cytological samples from the endometrial cavity

Background:Accumulating evidence suggests that many ovarian high-grade serous carcinomas (HGSCs) originate in the fallopian tube. Malignant cells shed by tubal lesions can be detected by examination of cytological samples from the endometrial cavity (endometrial cytological testing). To evaluate the use of this method for detecting HGSC, we examined epithelial ovarian, fallopian tube, and primary peritoneal cancer patients.Methods:Endometrial cytological testing was performed for endometrial cancer screening in asymptomatic women and for pre-treatment evaluation in symptomatic suspected ovarian, tubal, and peritoneal cancer patients.Results:Of the 122 ovarian, tubal, and peritoneal cancer patients, malignant cells were identified in 5 patients who did not show detectable abnormalities on imaging studies. Cervicovaginal cytology was positive in only one of these five patients. Four patients were asymptomatic and one was symptomatic. Three asymptomatic patients had early-stage HGSCs, and the other asymptomatic patient had positive peritoneal cytology findings but no detectable tumour. HGSC patients were significantly more likely to have positive findings on endometrial cytology than patients with other histological types (23% vs 6%, P=0.02).Conclusion:Endometrial cytological testing can detect early-stage ovarian, tubal, and peritoneal HGSCs without detectable pelvic masses and may be useful for ovarian cancer screening.

Endometrial cancer screening in Lynch syndrome: Do patients report symptoms prior to diagnosis?

Objective: With increasing awareness and testing for Lynch syndrome in patients with colorectal and endometrial cancer, an increasing number of individuals have been identified who carry germline mismatch repair (MMR) gene mutations. Current guidelines for endometrial cancer screening include annual endometrial sampling. The study objectives were to evaluate patient compliance with current screening guidelines and to evaluate symptoms before diagnosis of endometrial cancer in patients undergoing screening.

Screening endometrial cancer for Lynch syndrome in a Brazilian public health care system cancer center

Objective: Lynch syndrome (LS) is a hereditary cancer syndrome that increases the risk for colorectal and endometrial cancer (EC). To our best knowledge, our department is the first in Brazil with an organized screening program to select EC patients for genetic counseling in the context of the public health care system.

Endometrial and ovarian cancer in women with Lynch syndrome: update in screening and prevention

Women with Lynch syndrome have an additional need to address the substantial increased lifetime risk of endometrial and ovarian cancer. Endometrial or ovarian cancer can be the presenting cancer in individuals with Lynch syndrome, or can be a second cancer. Lifetime risk of endometrial cancer in women with MLH1 or MSH2 mutations is approximately 40%, with a median age of 49. Women with MSH6 mutations have a similar risk of endometrial cancer but a later age of diagnosis. Lynch syndrome-associated endometrial cancers are primarily endometrioid, although non-endometrioid subtypes including clear cell, papillary serous and MMMT have been reported. In addition, endometrial cancers arising in the lower uterine segment, while rare in the general population, are enriched in women with Lynch syndrome. Ovarian cancer risk in women with Lynch syndrome is 6-8%, and Lynch syndrome-associated ovarian cancers exhibit a variety of histopathological subtypes. Studies of endometrial cancer screening in Lynch syndrome have been small, and more recently have focused on the use of office endometrial biopsy to identify pre-malignant and early stage cancers. Prevention options include the use of oral contraceptives, which are known to be highly effective for decreasing risk of both endometrial and ovarian cancer in the general population, and prophylactic surgery to remove the uterus and ovaries.

Screening for gynecological cancers

An estimated 17% of all new cancers in women worldwide are due to cancers of the cervix, the ovary and the uterus. Together, these cancers account for 14.6% of all female cancer deaths. This is a significant societal and economic burden, which can be limited through cancer screening. In the developed world, marked reductions of 50–90% in disease rates have been observed as a result of cervical cancer screening. By contrast, in developing countries, where more than 85% of all new cases and deaths from this cancer are reported, significant challenges need to be overcome. Although cytology remains a key component of cervical screening, the newer molecular tests offer a more targeted, risk-attuned approach. The situation for the other two gynecological cancers is different. The case for ovarian cancer screening has yet to be made with the results of key screening trials in high- and low-risk populations still pending. Screening for endometrial cancer is traditionally not advocated as women become symptomatic ...