Lynch Syndrome In Women Research Articles

Universal screening for Lynch syndrome in endometrial cancer diagnoses in Auckland, New Zealand: The initial experience.

Universal mismatch repair immunohistochemistry (MMR IHC) tumour testing in endometrial cancer (EC) for Lynch syndrome (LS) was introduced in Auckland, New Zealand, in January 2017. Identifying patients with LS allows them and their families to access risk reduction strategies. Universal MMR IHC testing aids in the molecular classification of EC and has prognostic and therapeutic implications. We aimed to determine the incidence of LS in women with EC in Auckland, New Zealand, following the introduction of MMR testing and the impact of universal screening on local genetic services. This is a retrospective clinicopathological evaluation of women with a new EC diagnosis referred to the Auckland Gynaecological Oncology Unit from 1/1/17 to 31/12/18. Patient data were extracted from the Gynaecological Oncology Unit database and electronic records, and analysed using descriptive statistics. During the study period, 409 patients were diagnosed with EC, with an over-representation of Pacific Islanders (32.5%). Of these, 82.6% underwent MMR IHC testing, 20% were MMR-deficient (MMRd), and 71% had somatic hypermethylation. The Pacific Islander population had a 64% (odds ratio 0.36, P = 0.005) reduction in the odds of having MMRd tumours compared with Europeans. Of the patients who underwent MMR IHC testing, 5.5% were referred to a genetic clinic for germline testing. LS was confirmed in eight patients (2.3%). LS was diagnosed in 2.3% of patients. There was an over-representation of Pacific Islanders in the EC group but not among those diagnosed with LS.

Heterogeneity in the psychosocial and behavioral responses associated with a diagnosis of suspected Lynch syndrome in women with endometrial cancer

BackgroundA suspected Lynch syndrome (SLS) diagnosis is made when a tumor exhibits DNA mismatch repair deficiency but cannot be definitively assigned to an inherited or non-inherited etiology. This diagnosis poses challenges for healthcare professionals, patients, and their families in managing future cancer risks and clinical care.MethodsThis qualitative study aimed to explore the psychosocial and behavioral responses of endometrial cancer (EC) patients receiving a SLS diagnosis (EC-SLS). Semi-structured telephone interviews were conducted with 15 EC-SLS women, transcribed, and thematically analyzed.ResultsMost who interpreted their result as negative for Lynch syndrome (LS) believed they were at population-level risk of cancer and felt happy and relieved. Many participants who interpreted their result as inconclusive/not definitive for LS were confused about their cancer risk and experienced negative emotions of anger and frustration. Despite variation in colorectal cancer screening recommendations reported by participants, most adhered to the advice given. Almost all participants communicated their genetic test result to immediate family members; however, communication of family cancer risk management advice was more limited due to most participants reporting not receiving family screening advice. A family history of cancer and a professional healthcare background influenced participants’ engagement in regular cancer screening.ConclusionThese findings highlight variability in the psychosocial and behavioral responses associated with EC-SLS, providing insight into how healthcare professionals can optimally manage and support such individuals.

Lynch Syndrome Identification in Endometrial Cancer Patients: Should Universal Screening be Used for all Histologies?

Background: There is an increased proportion of non-endometrioid histologies in Lynch syndrome-associated compared to sporadic endometrial cancer; however, screening recommendations do not differ between type I and type II cancers. Objective: Our objective was to examine the frequency of Lynch syndrome identified in type I and type II endometrial cancers and their associated characteristics. Methods: We reviewed patients with type I and type II endometrial cancer who were screened for Lynch Syndrome or referred for genetic testing according to an age and family history-based screening protocol. All patients were seen and treated at a large academic institution affiliated with a county safety-net hospital. Clinical, pathologic, immunohistochemistry, and germline genetic testing results were obtained as well as the choice of genetic screening approach, personal and family history, and compliance with testing were assessed. Results: 234 women with type I and 29 patients with type II endometrial cancer were identified. Lynch syndrome was diagnosed in a total of eight (3.4%) type I endometrial cancer patients, all identified after age-based tumor screening. In type II endometrial cancer group, three (10.3%) patients had Lynch syndrome. One was referred for testing after abnormal immunohistochemistry screening under age 60. The other two were >60 years old and identified after abnormal immunohistochemistry screening performed on physician’s request. Conclusion: Age-based screening may not diagnose Lynch Syndrome in women with type II endometrial cancers. Our findings underscore the need for a universal screening approach in patients with type II endometrial cancers, even in a low-resource population.

Brief family history questionnaire to screen for Lynch syndrome in women with newly diagnosed non-serous, non-mucinous ovarian cancers

ObjectivesWhile ovarian cancer is the third most common Lynch syndrome-associated cancer in women, there is no established screening strategy to identify Lynch syndrome in this population. The objective of this...

Performance characteristics of brief family history questionnaire to screen for Lynch syndrome in women with newly diagnosed ovarian cancers

<h3>Objectives:</h3> Ovarian cancer (OC) is the third most common Lynch syndrome (LS)-associated cancer in women but there is no established screening strategy to identify LS in this population. In centers without access to universal tumor immunohistochemistry (IHC) testing for mismatch repair (MMR) deficiency, family history may identify patients with OC suspected of LS, prompting a referral to genetic counseling. We have previously developed and shown that patient-administered 4-item brief Family History Questionnaire (bFHQ) can effectively identify women with confirmed LS in those with newly diagnosed endometrial cancers. The objective of this study was to assess whether bFHQ can be used as a screening tool to identify women with OC at high risk of LS. <h3>Methods:</h3> Prospective cohort study recruited women with newly diagnosed non-serous/non-mucinous OC from three cancer centers in Ontario, Canada. Participants completed bHFQ, extended Family History Questionnaire (eFHQ; encompassing Amsterdam II criteria, Society of Gynecologic Oncology 20-25% criteria and Ontario Ministry of Health criteria), IHC for MMR proteins and universal germline testing (reference standard) for LS. The sensitivity, specificity, positive and negative predictive values (PPV, NPV) were compared between the family history screening strategies and MMR IHC to identify LS. <h3>Results:</h3> Of 215 women, 169 (79%) were evaluable with both bFHQ and germline mutation status; 12 of these 169 were confirmed to have LS (7%). Median age was 53 years (range 21-71), and for all 12 patients with LS, OC was their sentinel malignancy (100%). Nine of 12 patients (75%) with LS were correctly identified by bFHQ, compared to 6 of 11 (55%) by eFHQ and 11 of 13 (85%) by IHC. The sensitivity, specificity, PPV and NPV values of bFHQ were 75%, 66%, 15% and 98%, compared to 55%, 92%, 35% and 96% for eFHQ and 85%, 90%, 39% and 99% for IHC respectively (Table 1). IHC was the most sensitive and specific approach. The 4-item bFHQ was more sensitive than eFHQ and took less than 10 minutes for each patient to complete. <h3>Conclusions:</h3> Patient-administered bFHQ may serve as an adequate screening tool to triage women with OC for further genetic assessment for LS, especially in centers without access to universal tumor testing for IHC for MMR or microsatellite instability.

Performance characteristics of brief family history questionnaire to screen for Lynch syndrome in women with newly diagnosed ovarian cancers.

e22525 Background: Ovarian cancer (OC) is the third most common Lynch syndrome (LS)-associated cancer in women but there is no established screening strategy to identify LS in this population. An adequate family history may identify patients suspected of LS, prompting a referral to genetic assessment. We have previously validated the 4-item brief Family History Questionnaire (bFHQ) in endometrial cancers. The objective of this study was to assess whether bFHQ can be used as a screening tool to identify women with OC at risk of LS. Methods: Prospective cohort study recruited women with newly diagnosed non-serous/non-mucinous OC from three cancer centers in Ontario, Canada. Participants completed bHFQ, extended Family History Questionnaire (eFHQ; encompassing Amsterdam II criteria, Society of Gynecologic Oncology 20-25% criteria and Ontario Ministry of Health criteria), immunohistochemistry (IHC) for mismatch repair (MMR) proteins and universal germline testing for LS. The performance characteristics were compared between bFHQ, eFHQ, and IHC. Results: Of 215 participants, 169 (79%) were evaluable with both bFHQ and germline mutation status; 12 of these 169 were confirmed to have LS (7%). Nine of 12 patients (75%) with LS were correctly identified by bFHQ, compared to 6 of 11 (55%) by eFHQ and 11 of 13 (85%) by IHC. The sensitivity, specificity, positive predictive values and negative predictive values of bFHQ were 75%, 66%, 15% and 98%, compared to 55%, 92%, 35% and 96% for eFHQ and 85%, 90%, 39% and 99% for IHC respectively. IHC was the most sensitive and specific approach. The 4-item bFHQ was more sensitive than eFHQ and took less than 10 minutes for each patient to complete. Conclusions: Patient-administered bFHQ may serve as an adequate screening tool to triage women with OC for further genetic assessment for LS, especially in centers without access to universal tumor testing for IHC for MMR.[Table: see text]

Lynch syndrome for the gynaecologist.

Key content Lynch syndrome is an autosomal dominant condition closely associated with colorectal, endometrial and ovarian cancer.Women with Lynch syndrome are at increased risk of both endometrial and ovarian cancer and should be offered personalised counselling regarding family planning, red flag symptoms and risk‐reducing strategies.Surveillance for gynaecological cancer in women with Lynch syndrome remains controversial; more robust data are needed to determine its effectiveness.Universal testing for Lynch syndrome in endometrial cancer is being adopted by centres across Europe and is now recommended by the National Institute for Health and Care Excellence; thus, gynaecologists must become familiar with testing strategies and their results.Testing strategies involve risk stratification of cancers based on phenotypical features and definitive germline testing. Learning objectives To define the pathogenesis of Lynch syndrome and its associated gynaecological cancers.To understand the testing strategies for Lynch syndrome in women with gynaecological cancer.To learn how best to counsel women with Lynch syndrome regarding gynaecological cancer and risk‐reducing strategies to enable informed decision‐making. Ethical issues Offering gynaecological surveillance despite a lack of robust evidence for its clinical effectiveness may falsely reassure women and delay risk‐reducing hysterectomy.Genetic testing may yield variants of unknown significance with ill‐defined clinical implications, which can lead to confusion and anxiety.Genetic testing has implications not only for the individual, but also for the whole family, so expert counselling is crucial.

Prevalence of Lynch syndrome in women with mismatch repair-deficient ovarian cancer.

BackgroundThere are limited data on the prevalence of Lynch syndrome (LS) in women with primary ovarian cancer with mismatch repair deficiency (MMR‐D) by immunohistochemistry (IHC).Materials and MethodsThree hundred and eight cases of primary ovarian, fallopian, and peritoneal cancer between January 2012 and December 2019 were evaluated for MMR‐D by IHC. The incidence of LS in this cohort was evaluated.ResultsMMR‐D by IHC was identified in 16 of 308 (5.2%) (95% CI: 3.2%–8.3%) primary ovarian‐related cancers. Most cases with MMR‐D were endometrioid (n = 11, 68.7%); (95% CI: 44.2%–86.1%). MSH2/MSH6 protein loss was detected in eight cases (50.0%); (95% CI: 28.0%–72.0%) and MLH1/PMS2 protein loss was detected in four cases (25.0%); (95% CI: 9.7%–50.0%). MSH6 protein loss was detected in two cases (12.5%); (95% CI: 2.2%–37.3%) and PMS2 protein loss was detected in two cases (12.5%); (95% CI: 2.2%–37.3%). All four cases with MLH1/PMS2 protein loss had MLH1 promotor hypermethylation. All 12 women with ovarian cancer suggestive of LS underwent germline testing and 8 (66.6%); (95% CI: 38.8%–86.5%) were confirmed to have LS.ConclusionsMost ovarian cancers with somatic MMR‐D were confirmed to have LS in this cohort. Germline testing for LS in addition to BRCA1/2 for all women with an epithelial ovarian cancer would be efficient and would approach 100% sensitivity for identifying Lynch syndrome. Utilization of a multigene panel should also be considered, given the additional non‐Lynch germline mutation identified in this cohort.

Implementation of a quality improvement (QI) project of universal screening for Lynch syndrome in women with uterine cancer

Objective: The aim of this study was to determine the effectiveness of a quality improvement (QI) initiative to adopt universal screening for Lynch syndrome in women with uterine cancer at our institution.

Assessment of strategies to identify Lynch syndrome in women with synchronous endometrial and ovarian cancers

Objective: Synchronous endometrial and ovarian cancers are reported in 5%–10% of endometrial or ovarian cancers, but the incidence of Lynch syndrome and the optimal strategy to identify it is not well established in this population. Most centers favor reflex mismatch repair (MMR) testing of the endometrial cancer only. We aim to examine the proportion of cases that are MMR-deficient (MMRd) or microsatellite-instable (MSI-H) in the endometrium and ovary and assess the concordance between the 2 tumor sites.

Performance characteristics of screening strategies to identify Lynch syndrome in women with non-serous and non-mucinous ovarian cancer

Objective: The third most common cancer for women with Lynch syndrome (LS) is nonserous/nonmucinous ovarian cancer (OC). The incidence of LS and the optimal method for identifying LS in women with newly diagnosed OC has not been determined. We compared the performance characteristics between immunohistochemistry (IHC) for MMR proteins, microsatellite instability (MSI), and family history compared to germline mutation status to determine the best strategy to identify LS in this population.

The proportion of endometrial tumours associated with Lynch syndrome (PETALS): A prospective cross-sectional study

BackgroundLynch syndrome (LS) predisposes to endometrial cancer (EC), colorectal cancer, and other cancers through inherited pathogenic variants affecting mismatch-repair (MMR) genes. Diagnosing LS in women with EC can reduce subsequent cancer mortality through colonoscopic surveillance and aspirin chemoprevention; it also enables cascade testing of relatives. A growing consensus supports LS screening in EC; however, the expected proportion of test positives, and optimal testing strategy is uncertain. Previous studies from insurance-based healthcare systems were limited by narrow selection criteria, failure to apply reference standard tests consistently, and poor conversion to definitive testing. The aim of this study was to establish the prevalence of LS and the diagnostic accuracy of LS testing strategies in an unselected EC population.Methods and findingsThis was a prospective cross-sectional study carried out at a large United Kingdom gynaecological cancer centre between October 2015 and January 2017. Women diagnosed with EC or atypical hyperplasia (AH) were offered LS testing. Tumours underwent MMR immunohistochemistry (IHC), microsatellite instability (MSI), and targeted MLH1-methylation testing. Women <50 years, with strong family histories and/or indicative tumour molecular features, underwent MMR germline sequencing. Somatic MMR sequencing was performed when indicative molecular features were unexplained by LS or MLH1-hypermethylation. The main outcome measures were the prevalence of LS in an unselected EC population and the diagnostic accuracy of clinical and tumour testing strategies for risk stratifying women with EC for MMR germline sequencing. In total, 500 women participated in the study; only 2 (<1%) declined. Germline sequencing was indicated and conducted for 136 and 135 women, respectively. A total of 16/500 women (3.2%, 95% CI 1.8% to 5.1%) had LS, and 11 more (2.2%) had MMR variants of uncertain significance. Restricting testing to age <50 years, indicative family history (revised Bethesda guidelines or Amsterdam II criteria) or endometrioid histology alone would have missed 9/16 (56%), 8/13 (62%) or 9/13 (69%), and 5/16 (31%) cases of LS, respectively. In total 132/500 tumours were MMR deficient by IHC of which 83/132 (63%) had MLH1-hypermethylation, and 16/49 (33%) of the remaining patients had LS (16/132 with MMR deficiency, 12%). MMR-IHC with targeted MLH1-methylation testing was more discriminatory for LS than MSI with targeted methylation testing, with 100% versus 56.3% (16/16 versus 9/16) sensitivity (p = 0.016) and equal 97.5% (468/484) specificity; 64% MSI-H and 73% MMR deficient tumours unexplained by LS or MLH1-hypermethylation had somatic MMR mutations. The main limitation of the study was failure to conduct MMR germline sequencing for the whole study population, which means that the sensitivity and specificity of tumour triage strategies for LS detection may be overestimated, although the risk of LS in women with no clinical or tumour predictors is expected to be extremely low.ConclusionsIn this study, we observed that age, family history, and histology are imprecise clinical correlates of LS-EC. IHC outperformed MSI for tumour triage and reliably identified both germline and somatic MMR mutations. The 3.2% proportion of LS-EC is similar to colorectal cancer, supporting unselected screening of EC for LS.

Performance characteristics of screening strategies to identify Lynch syndrome in women with ovarian cancer.

BackgroundFor women with ovarian cancer (OC), the optimal screening strategy to identify Lynch syndrome (LS) has not been determined. In the current study, the authors compared the performance characteristics of various strategies combining mismatch repair (MMR) immunohistochemistry (IHC), microsatellite instability testing (MSI), and family history for the detection of LS.MethodsWomen with nonserous and/or nonmucinous ovarian cancer were recruited prospectively from 3 cancer centers in Ontario, Canada. All underwent germline testing for LS and completed a family history assessment. Tumors were assessed using MMR IHC and MSI. The sensitivity, specificity, and positive and negative predictive values of screening strategies were compared with the gold standard of a germline result.ResultsOf 215 women, germline data were available for 189 (88%); 13 women (7%) had pathogenic germline variants with 7 women with mutS homolog 6 (MSH6); 3 women with mutL homolog 1 (MLH1); 2 women with PMS1 homolog 2, mismatch repair system component (PMS2); and 1 woman with mutS homolog 2 (MSH2). A total of 28 women had MMR‐deficient tumors (13%); of these, 11 had pathogenic variants (39%). Sequential IHC (with MLH1 promoter methylation analysis on MLH1‐deficient tumors) followed by MSI for nonmethylated and/or MMR‐intact patients was the most sensitive (92.3%; 95% confidence interval, 64%‐99.8%) and specific (97.7%; 95% confidence interval, 94.2%‐99.4%) approach, missing 1 case of LS. IHC with MLH1 promoter methylation analysis missed 2 patients of LS. Family history was found to have the lowest sensitivity at 55%.ConclusionsSequential IHC (with MLH1 promoter methylation analysis) followed by MSI was found to be most sensitive. However, IHC with MLH1 promoter methylation analysis also performed well and is likely more cost‐effective and efficient in the clinical setting. The pretest probability of LS is high in patients with MMR deficiency and warrants universal screening for LS.

Cost-Effectiveness of the Manchester Approach to Identifying Lynch Syndrome in Women with Endometrial Cancer.

Lynch syndrome (LS) is a hereditary cancer syndrome responsible for 3% of all endometrial cancer and 5% in those aged under 70 years. It is unclear whether universal testing for LS in endometrial cancer patients would be cost-effective. The Manchester approach to identifying LS in endometrial cancer patients uses immunohistochemistry (IHC) to detect mismatch repair (MMR) deficiency, incorporates testing for MLH1 promoter hypermethylation, and incorporates genetic testing for pathogenic MMR variants. We aimed to assess the cost-effectiveness of the Manchester approach on the basis of primary research data from clinical practice in Manchester. The Proportion of Endometrial Tumours Associated with Lynch Syndrome (PETALS) study informed estimates of diagnostic performances for a number of different strategies. A recent microcosting study was adapted and was used to estimate diagnostic costs. A Markov model was used to predict long-term costs and health outcomes (measured in quality-adjusted life years, QALYs) for individuals and their relatives. Bootstrapping and probabilistic sensitivity analysis were used to estimate the uncertainty in cost-effectiveness. The Manchester approach dominated other reflex testing strategies when considering diagnostic costs and Lynch syndrome cases identified. When considering long-term costs and QALYs the Manchester approach was the optimal strategy, costing £5459 per QALY gained (compared to thresholds of £20,000 to £30,000 per QALY commonly used in the National Health Service (NHS)). Cost-effectiveness is not an argument for restricting testing to younger patients or those with a strong family history. Universal testing for Lynch syndrome in endometrial cancer patients is expected to be cost-effective in the U.K. (NHS), and the Manchester approach is expected to be the optimal testing strategy.

Examining patterns of genetic evaluation as well as the prevalence of tumor Mismatch Repair Deficiency or Microsatellite Instability and Lynch Syndrome in Women with Endometrial Cancer in New Orleans

Examining patterns of genetic evaluation as well as the prevalence of tumor Mismatch Repair Deficiency or Microsatellite Instability and Lynch Syndrome in Women with Endometrial Cancer in New Orleans

Cost-effectiveness analysis of reflex testing for Lynch syndrome in women with endometrial cancer in the UK setting.

BackgroundLynch syndrome is a hereditary cancer syndrome caused by constitutional pathogenic variants in the DNA mismatch repair (MMR) system, leading to increased risk of colorectal, endometrial and other cancers. The study aimed to identify the incremental costs and consequences of strategies to identify Lynch syndrome in women with endometrial cancer.MethodsA decision-analytic model was developed to evaluate the relative cost-effectiveness of reflex testing strategies for identifying Lynch syndrome in women with endometrial cancer taking the NHS perspective and a lifetime horizon. Model input parameters were sourced from various published sources. Consequences were measured using quality-adjusted life years (QALYs). A cost-effectiveness threshold of £20 000/QALY was used.ResultsReflex testing for Lynch syndrome using MMR immunohistochemistry and MLH1 methylation testing was cost-effective versus no testing, costing £14 200 per QALY gained. There was uncertainty due to parameter imprecision, with an estimated 42% chance this strategy is not cost-effective compared with no testing. Age had a significant impact on cost-effectiveness, with testing not predicted to be cost-effective in patients aged 65 years and over.ConclusionsTesting for Lynch syndrome in younger women with endometrial cancer using MMR immunohistochemistry and MLH1 methylation testing may be cost-effective. Age cut-offs may be controversial and adversely affect implementation.

Comparison of effectiveness of two strategies to identify Lynch Syndrome in women with endometrial cancer

Comparison of effectiveness of two strategies to identify Lynch Syndrome in women with endometrial cancer

Lynch syndrome in women with endometrial cancer: Comparison of universal and age-based strategies in a California healthcare system

Lynch syndrome in women with endometrial cancer: Comparison of universal and age-based strategies in a California healthcare system

Interobserver Agreement for Mismatch Repair Protein Immunohistochemistry in Endometrial and Nonserous, Nonmucinous Ovarian Carcinomas.

Immunohistochemistry (IHC) for mismatch repair (MMR) proteins is an established test to identify Lynch syndrome (LS) in patients with colorectal cancer and is being increasingly used to identify LS in women with endometrial and/or nonserous ovarian cancer (OC). We assessed interobserver agreement in the interpretation of MMR-IHC on endometrial and ovarian carcinomas. The study consisted of 73 consecutive endometrial cancers (n=48) and nonserous, nonmucinous epithelial OCs (n=25). Six pathologists from 2 cancer centers, one with and the other without, previous experience in interpreting MMR-IHC, evaluated MLH1, MSH2, MSH6, and PMS2 stains. Before the study, an experienced pathologist led a review of 9 teaching cases. A decision tool was developed as a guide in MMR-IHC interpretation. Staining was interpreted as intact, deficient, or equivocal for each protein. Interobserver agreement for the patient MMR status was categorized as "almost perfect" with κ=0.919 (95% CI, 0.863-0.976). All observers were in agreement in 66 (92%) tumors. Four of the less experienced pathologists had at least 1 discrepant interpretation. There were 6 discordant cases: 3 MMR-deficient cases and 2 MMR-intact cases by majority opinion were called equivocal by at least 1 observer, and 1 MMR-deficient case by majority opinion was interpreted as MMR intact by 1 pathologist. Only the latter case (1/73 patients, 1.4%) had an unequivocal disagreement that could affect patient management. Issues associated with discordant interpretation included heterogeneous staining, intratumoral lymphocytes, regional reduced internal control tissue staining, and scattered absent/weak staining adjacent to tumor cells with strong nuclear staining.

The prevalence of Lynch syndrome in women with endometrial cancer: a systematic review protocol

BackgroundLynch syndrome is the most common inherited cancer syndrome, which predisposes individuals to a number of different cancers, principally colorectal and endometrial cancer. The early diagnosis of Lynch syndrome enables colorectal surveillance, which has been shown to save lives through the detection and removal of premalignant polyps and earlier detection of invasive disease. Endometrial cancer, which is often the sentinel cancer in women, provides an opportunity to diagnose Lynch syndrome and thus enable colorectal surveillance as well as the cascade testing for Lynch syndrome in other family members. These potential benefits have led to a call for the universal screening of women with endometrial cancer for Lynch syndrome, a practice that is now commonplace in colorectal cancer. Healthcare providers and clinicians are however restricted by insufficient knowledge about the prevalence of Lynch syndrome in women with endometrial cancer, with estimates varying as widely as 1–10%. The aim of this study is to perform a systematic review with a meta-analysis of the current literature base in order to estimate the prevalence of Lynch syndrome among women with endometrial cancer to inform this discussion.MethodsMedline, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), Cochrane Methodology Register, NHS Health and Technology Assessment Database and the Web of Science will be systematically searched for relevant studies via the Ovid platform. Two authors will review the titles and abstracts independently, with discrepancy settled by a third author. Data extraction will be completed to record demographic, pathological and clinical data, as well as the diagnostic methods used for estimating the prevalence of Lynch syndrome in women with endometrial cancer. Bias will be assessed and recorded using the Newcastle-Ottawa Scale and that of the International Cochrane Collaboration. Dependent on the heterogeneity of the data, we aim to produce a cumulative incidence in addition to subgroup analyses as to investigate secondary outcomes.DiscussionThe aim of this systematic review is to provide a robust estimate of the prevalence of Lynch syndrome in women with endometrial cancer. This will enable resource allocation and decision-making regarding the appropriateness of screening all women, or certain women, with endometrial cancer for Lynch syndrome. Such a policy could enable the earlier diagnosis of Lynch syndrome in women and, through the application of colorectal cancer surveillance, improve their survival outcomes.Systematic review registrationThis systematic review has been registered on PROSPERO (ref CRD42017081707).