scholarly journals 373 A Review of Microsatellite Instability (MSI) Testing: Real World Clinical Data

2021 ◽  
Vol 108 (Supplement_2) ◽  
Author(s):  
C Harris ◽  
I McCallum ◽  
S Mills
Keyword(s):  
High Risk ◽  
Lynch Syndrome ◽  
Microsatellite Instability ◽  
Treatment Options ◽  
Prognostic Information ◽  
Screening And Surveillance ◽  
Familial Cancers ◽  
The Mean ◽  
The Uk ◽  
Msi Analysis

Abstract Introduction Colorectal cancers (CRC) are the second most common cause of death by cancer, in the UK. Microsatellite instability (MSI) analysis is novel yet important part of managing CRC and used as a tool for predicting prognosis, treatment and identifying lynch syndrome. Where lynch syndrome is identified, preventative screening can be utilised. Previous studies only focused tumour testing on high-risk cases. Method A retrospective study at Northumbria Health Care NHS Trust was performed on all new CRC patients between 2017-2020. Results A total of 965 patients with CRC were identified. After exclusion criteria was applied to the cohort, a total of 483 patients were identified as having undergone MSI analysis. The mean age was 73.5 years old, with the female to male ratio being 1:1.4. Patients were further grouped into MSI stable, low, and high. MSI High patients accounted for 10% of patients analysed. Further genetic testing was performed on these patients which highlighted 28 patients with BRAF positive genes who went on to screening for Lynch syndrome associated cancers. Conclusions MSI testing provides essential diagnostic, prognostic information and also guides treatment options. 2.9% of patients identified as high risk for familial cancers and went on to have genetic screening and surveillance.

Prospective Determination of Prevalence of Lynch Syndrome in Young Women With Endometrial Cancer

2007 ◽  
Vol 25 (33) ◽  
pp. 5158-5164 ◽  
Author(s):  
Karen H. Lu ◽  
John O. Schorge ◽  
Kerry J. Rodabaugh ◽  
Molly S. Daniels ◽  
Charlotte C. Sun ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Lynch Syndrome ◽  
Microsatellite Instability ◽  
Germline Mutation ◽  
Age Of Onset ◽  
Cancer Syndrome ◽  
Degree Relative ◽  
Entire Cohort ◽  
Tumor Studies ◽  
The Mean

Purpose Age younger than 50 years at the time of colon cancer diagnosis is often used as a screening criterion for Lynch syndrome (hereditary nonpolyposis colorectal cancer syndrome). The purpose of this study was to determine the prevalence of MLH1, MSH2, and MSH6 mutations in an unselected cohort of women diagnosed with endometrial cancer at age younger than 50 years. Methods A prospective, multicenter study was performed at three institutions. After written consent was obtained, germline mutation testing by full sequencing and large deletion analysis of the MLH1, MSH2, and MSH6 genes was performed. Tumor studies included immunohistochemistry of MLH1, MSH2, and MSH6; microsatellite instability analysis; and hypermethylation of the MLH1 promoter. Results Of the 100 women, nine (9%; 95% CI, 4.2 to 16.4) carried a deleterious germline mutation: seven women with mutations in MSH2, one woman with a mutation in MLH1, and one woman with a mutation in MSH6. Two additional women had molecular studies consistent with the diagnosis of Lynch syndrome. The mean body mass index (BMI) for the entire cohort was 34.4, which is significantly higher than 29.2, the mean BMI for the mutation carriers. Predictors of finding a germline mutation included having a first-degree relative with a Lynch syndrome–associated cancer, endometrial tumor with loss of MSH2 expression, tumors with high microsatellite instability, and lower BMI. Conclusion In this prospective study of endometrial cancer patients younger than age 50 years, 9% were found to carry germline Lynch syndrome–associated mutations. In addition to young age of onset, family history, BMI, and molecular tumor studies can improve the likelihood of identifying a Lynch syndrome–associated germline mutation in MLH1, MSH2, and MSH6.

scholarly journals Failure in the application of fragility fracture prevention guidelines

2014 ◽  
Vol 96 (5) ◽  
pp. 381-385 ◽  
Author(s):  
MH Elvey ◽  
H Pugh ◽  
G Schaller ◽  
G Dhotar ◽  
B Patel ◽  
...  
Keyword(s):  
Hip Fracture ◽  
High Risk ◽  
Fragility Fracture ◽  
Fragility Fractures ◽  
Fracture Prevention ◽  
Consecutive Series ◽  
National Guidelines ◽  
Fracture Population ◽  
The Mean ◽  
The Uk

Introduction The cost of fragility fractures to the UK economy is predicted to reach £2.2 billion by 2025. We studied our hip fracture population to establish whether national guidelines on fragility fracture prevention were being followed, and whether high risk patients were identified and treated by local care services. Methods Data on a consecutive series of trauma hip fracture admissions were collected prospectively over 14 months. National Institute for Health and Care Excellence (NICE) and National Osteoporosis Guideline Group (NOGG) recommendations and FRAX® risk calculations were applied to patients prior to their admission with a new hip fracture. Results Overall, 94 patients were assessed against national guidelines. The mean population age was 77 years. Almost a quarter (22%) of patients had suffered a previous fragility fracture. The mean FRAX® ten-year probability of hip fracture was 7%. According to guidelines, 45% of the study population required treatment, 35% fulfilled criteria for investigation and reassessment, and 20% needed no further management. In practice, 27% received treatment, 4% had undergone dual energy x-ray absorptiometry and were untreated, and 69% had not been investigated and were untreated. In patients meeting intervention thresholds, only 33% of those who required treatment were receiving treatment in practice. Conclusions In conjunction with NICE and NOGG recommendations, FRAX® was able to identify 80% of our fracture population as intermediate or high risk on the day of fracture. Correct management was evident in a third of cases with a pattern of inferior guideline compliance seen in a London population. There remains a lack of clarity over the duty of care in fragility fracture prevention.

T2040 Poor Compliance with MSI-Analysis in Patients with Colorectal Cancer At High Risk for Lynch Syndrome

2008 ◽  
Vol 134 (4) ◽  
pp. A-606
Author(s):  
Margot G. van Lier ◽  
J. de Wilt ◽  
J. Wagemakers ◽  
W. Dinjens ◽  
R. Damhuis ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
High Risk ◽  
Lynch Syndrome ◽  
Poor Compliance ◽  
Msi Analysis

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]

S1979 Routine MSI-Analysis in Colorectal Cancer Patients ≥ 70 Years Leads to the Identification of More Patients At High Risk for Lynch Syndrome

2009 ◽  
Vol 136 (5) ◽  
pp. A-306
Author(s):  
Margot G. van Lier ◽  
A. Wagner ◽  
Ernst J. Kuipers ◽  
W. Dinjens ◽  
M.E. Leerdam van ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
High Risk ◽  
Lynch Syndrome ◽  
Cancer Patients ◽  
Colorectal Cancer Patients ◽  
Msi Analysis

S1981 Routine MSI-Analysis in Advanced Adenomas in Patients Younger Than 45 Years Leads to the Identification of More Patients at High Risk for Lynch Syndrome

2010 ◽  
Vol 138 (5) ◽  
pp. S-294
Author(s):  
Celine H. Leenen ◽  
Margot G. van Lier ◽  
Anja Wagner ◽  
W. Dinjens ◽  
Erik-Jan Dubbink ◽  
...  
Keyword(s):  
High Risk ◽  
Lynch Syndrome ◽  
Advanced Adenomas ◽  
Msi Analysis

Underutilization of microsatellite instability analysis in colorectal cancer patients at high risk for Lynch syndrome

2009 ◽  
Vol 44 (5) ◽  
pp. 600-604 ◽  
Author(s):  
Margot G. F. Van Lier ◽  
Johannes H. W. De Wilt ◽  
Jessie J. M. F. Wagemakers ◽  
Winand N. M. Dinjens ◽  
Ronald A. M. Damhuis ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
High Risk ◽  
Lynch Syndrome ◽  
Microsatellite Instability ◽  
Cancer Patients ◽  
Instability Analysis ◽  
Colorectal Cancer Patients ◽  
Microsatellite Instability Analysis

TUMOUR PATHOLOGY PREDICTS MICROSATELLITE INSTABILITY IN A POPULATION-BASED SERIES OF COLORECTAL CANCER CASES

2008 ◽  
Vol 31 (4) ◽  
pp. 12
Author(s):  
A J Hyde ◽  
D Fontaine ◽  
R C Green ◽  
M Simms ◽  
P S Parfrey ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Lynch Syndrome ◽  
Microsatellite Instability ◽  
Population Based ◽  
Pathological Features ◽  
Predictive Tool ◽  
Entire Cohort ◽  
Dna Mismatch ◽  
Bethesda Guidelines ◽  
Revised Bethesda Guidelines

Background: Lynch Syndrome is an autosomal dominant trait that accounts forapproximately 3% of all cases of colorectal cancer (CRC). It is caused by mutations in DNA mismatch repair (MMR) genes, most commonly MLH1 or MSH2. These MMR defects cause high levels of microsatellite instability (MSI-H) in the tumours. MSI testing of all CRCs to identify potential Lynch Syndrome cases is not practical, so the Bethesda Guidelines, which use clinical and pathological features, were created to identify those tumours most likely to be MSI-H^1. In 2007 Jenkins et. al. created MsPath, a tool based on the pathological features described in the rarely used 3^rd Bethesda criterion, to improve prediction of MSI-H tumours among CRC cases diagnosed before age 60 years^2. Methods: We collected a population-based cohort of 716 CRC cases diagnosed before age 75 years in Newfoundland. For each of these cases we collected family history, performed MSI analysis, and scored a number of pathological features for the purpose of evaluating the accuracy of the Bethesda Criteria and MsPath at predicting MSI-H tumours. Results: Our work validates the MsPath tool in the Newfoundland population for the same age group used to create the tool. We found it identified MSI-H cases with a sensitivity of 95% and specificity of 35% in our population of CRCcases diagnosed before age 60 years (n=290). We also tested this tool on our older population of CRCcases, diagnosed at ages 60 to 74 years (n=426). We found it to be at least as predictive in this population,with a sensitivity of 95% and a specificity of 42%. We then used our entire cohort (N=716) to compare MsPath with the other Bethesda criteria.Bethesda criteria 1, 2, 4 and 5 together predicted MSI-H cases with a sensitivity of 67% and a specificity of 51%. MsPath was better at identifying these cases, with a sensitivity of 95% and a specificity of 39%. Conclusions: We conclude that MsPath can be extended to include patients diagnosed with CRC before age 75 years. As well, we have found that MsPath is a better predictive tool than the Revised Bethesda Guidelines for identifying MSI-H cases within a population-based setting of colorectal cancer. References: 1. Umar, A. et. al. J Natl Cancer Inst 2004;96:261-8 2.Jenkins, M.A. et. al. Gastroenterology 2007;133:48-56

scholarly journals COVID-19 in a Cohort of Patients with Congenital Myasthenic Syndrome

2021 ◽  
pp. 1-3
Author(s):  
Setareh Alabaf ◽  
Karen O'Connell ◽  
Sithara Ramdas ◽  
David Beeson ◽  
Jacqueline Palace
Keyword(s):  
High Risk ◽  
Neuromuscular Transmission ◽  
Genetic Disorders ◽  
Severe Disease ◽  
Congenital Myasthenic Syndrome ◽  
Referral Centre ◽  
History Of ◽  
Myasthenic Syndrome ◽  
The Uk ◽  
Rare Group

Congenital Myasthenic Syndrome (CMS) are a rare group of genetic disorders of neuromuscular transmission. Some subtypes of CMS can be associated with respiratory and bulbar weakness and these patients may therefore be at high risk of developing a severe disease from COVID-19. We screened 73 patients with genetically confirmed CMS who were attending the UK national referral centre for evidence of previous Severe Acute Respiratory Syndrome Corona Virus 2 infection and their clinical outcome. Of 73 patients, seven had history of confirmed COVID-19. None of the infected patients developed a severe disease, and there were no signals that CMS alone carries a high risk of severe disease from COVID-19.

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