scholarly journals Utility of MLH1 Methylation Analysis in the Clinical Evaluation of Lynch Syndrome in Women with Endometrial Cancer

2014 ◽  
Vol 20 (11) ◽  
pp. 1655-1663 ◽  
Author(s):  
Amanda Bruegl ◽  
Bojana Djordjevic ◽  
Diana Urbauer ◽  
Shannon Westin ◽  
Pamela Soliman ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Lynch Syndrome ◽  
Clinical Evaluation ◽  
Methylation Analysis ◽  
Mlh1 Methylation

Universal endometrial cancer tumor typing: How much has immunohistochemistry, microsatellite instability, and MLH1 methylation improved the diagnosis of Lynch syndrome across the population?

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e17119-e17119
Author(s):  
Ryan Kahn ◽  
Sushmita Gordhandas ◽  
Brandon Paul Maddy ◽  
Becky Baltich Nelson ◽  
Gulce Askin ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Lynch Syndrome ◽  
Microsatellite Instability ◽  
Large Scale ◽  
Screening Method ◽  
Cochrane Library ◽  
Predictive Values ◽  
Msi Analysis ◽  
Weighted Prevalence ◽  
Mlh1 Methylation

e17119 Background: Universal tumor testing for defective DNA mismatch repair (MMR) is recommended for all women diagnosed with endometrial cancer (EC) to identify those with underlying Lynch syndrome (LS). However, since its implementation in 2013, the effectiveness of this screening method on identifying individuals with LS across the population has not been well studied. The aim of this study was to evaluate outcomes of MMR immunohistochemistry (IHC), MLH1 methylation, and microsatellite instability (MSI) analysis among EC patients. Methods: We conducted a complete systematic search of online databases PubMed, Embase, Medline, and Cochrane Library between 1990-2018. A DerSimonian–Laird random-effects model meta-analysis was utilized to estimate the weighted prevalence of LS diagnoses. Results: The comprehensive search produced 3,427 publications. 29 peer-review studies met the inclusion criteria. 6,649 EC patients were identified, 206 (3%) were confirmed to have LS following positive universal tumor molecular screening.5,917 patients underwent tumor IHC, 28% had abnormal staining. 3,140 patients underwent MSI analysis, 31% had MSI instability. Among EC patients with deficient IHC staining or positive MSI analysis, the weighted prevalence of LS was 15% and 19% respectively. 1159 patients exhibited loss of MLH1 staining, 143 (13.7%) were found to be MLH1 methylation negative, 32 demonstrated a germline MLH1 mutation (2.8% of all MLH1 absent staining; 22.4% of all MLH1 methylation negative). 43% of EC patients diagnosed with LS via tumor typing would have been missed by family history-based screening alone. Conclusions: Despite widespread implementation of universal tumor testing in EC, data regarding results have previously been limited. For the first time, this study provides large-scale predictive values that will help practitioners evaluate abnormal results in the context of LS and aid in patient counseling. [Table: see text]

scholarly journals Combined Microsatellite Instability, MLH1 Methylation Analysis, and Immunohistochemistry for Lynch Syndrome Screening in Endometrial Cancers From GOG210: An NRG Oncology and Gynecologic Oncology Group Study

2015 ◽  
Vol 33 (36) ◽  
pp. 4301-4308 ◽  
Author(s):  
Paul J. Goodfellow ◽  
Caroline C. Billingsley ◽  
Heather A. Lankes ◽  
Shamshad Ali ◽  
David E. Cohn ◽  
...  
Keyword(s):  
Family History ◽  
Lynch Syndrome ◽  
Microsatellite Instability ◽  
Gynecologic Oncology ◽  
Gynecologic Oncology Group ◽  
Methylation Analysis ◽  
Screening Practice ◽  
Mutation Carriers ◽  
Number Of Patients ◽  
Mlh1 Methylation

Purpose The best screening practice for Lynch syndrome (LS) in endometrial cancer (EC) remains unknown. We sought to determine whether tumor microsatellite instability (MSI) typing along with immunohistochemistry (IHC) and MLH1 methylation analysis can help identify women with LS. Patients and Methods ECs from GOG210 patients were assessed for MSI, MLH1 methylation, and mismatch repair (MMR) protein expression. Each tumor was classified as having normal MMR, defective MMR associated with MLH1 methylation, or probable MMR mutation (ie, defective MMR but no methylation). Cancer family history and demographic and clinical features were compared for the three groups. Lynch mutation testing was performed for a subset of women. Results Analysis of 1,002 ECs suggested possible MMR mutation in 11.8% of tumors. The number of patients with a family history suggestive of LS was highest among women whose tumors were classified as probable MMR mutation (P = .001). Lynch mutations were identified in 41% of patient cases classified as probable mutation (21 of 51 tested). One of the MSH6 Lynch mutations was identified in a patient whose tumor had intact MSH6 expression. Age at diagnosis was younger for mutation carriers than noncarriers (54.3 v 62.3 years; P < .01), with five carriers diagnosed at age > 60 years. Conclusion Combined MSI, methylation, and IHC analysis may prove useful in Lynch screening in EC. Twenty-four percent of mutation carriers presented with ECs at age > 60 years, and one carrier had an MSI-positive tumor with no IHC defect. Restricting Lynch testing to women diagnosed at age < 60 years or to women with IHC defects could result in missing a substantial fraction of genetic disease.

Lynch syndrome-related non-endometrioid endometrial cancer: analysis of outcomes

2019 ◽  
Vol 30 (1) ◽  
pp. 56-61
Author(s):  
Giorgio Bogani ◽  
Maria Grazia Tibiletti ◽  
Maria Teresa Ricci ◽  
Ileana Carnevali ◽  
Viola Liberale ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Lynch Syndrome ◽  
Disease Free Survival ◽  
Oncologic Outcomes ◽  
Cox Models ◽  
Matching Algorithm ◽  
Pathogenic Variants ◽  
Propensity Matching ◽  
Endometrioid Endometrial Cancer

ObjectiveWomen with Lynch syndrome have a risk up to 40–60% of developing endometrial cancer, which is higher than their risk of developing colorectal or ovarian cancer. To date, no data on the outcomes of patients with Lynch syndrome diagnosed with non-endometrioid endometrial cancer are available. The goal of this study was to evaluate the outcome of patients with Lynch syndrome diagnosed with non-endometrioid endometrial cancer.MethodsData from consecutive patients diagnosed with Lynch syndrome and with a histological diagnosis of non-endometrioid endometrial cancer were retrospectively collected in two referral institutes in Italy. A case–control comparison (applying a propensity matching algorithm) was performed in order to compare patients with proven Lynch syndrome and controls. Inclusion criteria were: (a) histologically-proven endometrial cancer; (b) detection of a germline pathogenic variant in one of the MMR genes; (c) adequate follow-up. Only carriers of pathogenic or likely pathogenic variants (ie, class 5 and 4 according to the InSiGHT classification) were included in the study. Survival outcomes were assessed using KaplanMeier and Cox models.ResultsOverall, 137 patients with Lynch syndrome were collected. Mean patient age was 49.2 (10.9) years. Genes involved in the Lynch syndrome included MLH1, MSH2, and MSH6 in 43%, 39%, and 18% of cases, respectively. The study population included 27 patients with non-endometrioid endometrial cancer, who were matched 1:2 with patients with sporadic cancers using a propensity matching algorithm. After a median follow-up of 134 months (range 1–295), 2 (7.4%) of the 27 patients developed recurrent disease (3 and 36 months) and subsequently died of disease (7 and 91 months). Patients diagnosed with Lynch syndrome experienced better disease-free survival (HR 7.86 (95% CI 1.79 to 34.5); p=0.006) and overall survival (HR 5.33 (95% CI 1.18 to 23.9); p=0.029) than controls.ConclusionsNon-endometrioid endometrial cancer occurring in patients with Lynch syndrome might be associated with improved oncologic outcomes compared with controls. Genetic/molecular profiling should be investigated in order to better understand the mechanism underlying the prognosis.

scholarly journals Prospective Study of Combined Colon and Endometrial Cancer Screening in Women With Lynch Syndrome: A Patient-Centered Approach

2011 ◽  
Vol 7 (1) ◽  
pp. 43-47 ◽  
Author(s):  
Marilyn Huang ◽  
Charlotte Sun ◽  
Stephanie Boyd-Rogers ◽  
Jennifer Burzawa ◽  
Andrea Milbourne ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Cancer Screening ◽  
Lynch Syndrome ◽  
Prospective Study ◽  
Patient Centered

Combined colon and endometrial cancer screening is a patient-centered approach that is feasible and acceptable and may improve adherence to Lynch syndrome screening recommendations.

Adoption of universal next generation sequencing for lynch syndrome screening in endometrial cancer

2022 ◽  
Vol 164 (1) ◽  
pp. 4-5
Author(s):  
Isabel Rodriguez ◽  
Sarah Strickland ◽  
David Wells ◽  
Enna Manhardt ◽  
Eric Konnick ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Next Generation Sequencing ◽  
Lynch Syndrome ◽  
Next Generation ◽  
Generation Sequencing
Sign in / Sign up

Export Citation Format

Share Document