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

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.

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HIGH RISK PATIENTS SUSPICIOUS OF LYNCH SYNDROME; ARE THEY BEING CLASSIFIED CORRECTLY AND RECEIVING APPROPRIATE SURVEILLANCE?

10.1055/s-0040-1704467 ◽

2020 ◽

Author(s):

T Ryan ◽

S Foy ◽

J Leyden ◽

P MacMathuna ◽

NM Farrelly ◽

...

Keyword(s):

High Risk ◽

Lynch Syndrome ◽

High Risk Patients ◽

Risk Patients

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Performance of tumor testing for Lynch syndrome identification in patients with colorectal cancer: A retrospective single-center study

Tumori Journal ◽

10.1177/0300891618792460 ◽

2018 ◽

Vol 105 (1) ◽

pp. 76-83 ◽

Cited By ~ 3

Author(s):

Stefano Signoroni ◽

Maria Grazia Tibiletti ◽

Maria Teresa Ricci ◽

Massimo Milione ◽

Federica Perrone ◽

...

Keyword(s):

Colorectal Cancer ◽

Lynch Syndrome ◽

Characteristic Curve ◽

Age At Onset ◽

Area Under The Curve ◽

Single Center ◽

Germline Variants ◽

Amsterdam Criteria ◽

Clinicopathologic Parameters ◽

Msi Analysis

Objective: To investigate the performance of tumor testing approaches in the identification of Lynch syndrome (LS) in a single-center cohort of people with colorectal cancer (CRC). Methods: A retrospective analysis of data stored in a dedicated database was carried out to identify patients with CRC suspected for LS who were referred to Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy, between 1999 and 2014. The sensitivity and specificity of immunohistochemistry (IHC) for mismatch repair (MMR) proteins and microsatellite instability (MSI) analysis (alone or combined) were calculated with respect to the presence of causative MMR germline variants. Results: A total of 683 patients with CRC suspected for LS were identified. IHC results of MMR protein analysis and MSI were assessed in 593 and 525 CRCs, respectively, while germline analysis was performed in 418 patients based on the IHC or MSI test result and/or clinical features. Univariate and multivariate analysis revealed a significant correlation of pathogenic MMR germline variants with all clinicopathologic features including Amsterdam criteria, presence of endometrial cancer, CRC site, age at onset, stage, and grade. The highest odds ratio values were observed for IHC and MSI (17.1 and 8.8, respectively). The receiver operating characteristic curve and area under the curve values demonstrated that IHC alone or combined with other clinicopathologic parameters was an excellent test for LS identification. Conclusions: This study confirms the effectiveness of tumor testing to identify LS among patients with CRC. Although IHC and MSI analysis were similarly effective, IHC could be a better strategy for LS identification as it is less expensive and more feasible.

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Gynecologic cancer screening in women at high risk of Lynch syndrome.

Journal of Clinical Oncology ◽

10.1200/jco.2011.29.15_suppl.1559 ◽

2011 ◽

Vol 29 (15_suppl) ◽

pp. 1559-1559 ◽

Cited By ~ 1

Author(s):

C. Guillen-Ponce ◽

C. Martinez-Sevila ◽

R. Perea ◽

M. Arenas ◽

M. J. Molina-Garrido ◽

...

Keyword(s):

Cancer Screening ◽

High Risk ◽

Lynch Syndrome ◽

Gynecologic Cancer

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NCCN Increases the Emphasis on Genetic/Familial High-Risk Assessment in Colorectal Cancer

Journal of the National Comprehensive Cancer Network ◽

10.6004/jnccn.2014.0200 ◽

2014 ◽

Vol 12 (5S) ◽

pp. 829-831 ◽

Cited By ~ 22

Author(s):

Heather Hampel

Keyword(s):

Colorectal Cancer ◽

Risk Assessment ◽

High Risk ◽

Lynch Syndrome ◽

Risk Reduction ◽

Hereditary Colorectal Cancer ◽

Clinical Criteria ◽

New Guidelines ◽

Familial High Risk

NCCN has developed new guidelines for the assessment of high-risk familial/genetic colorectal cancer, and has positioned these recommendations within the guidelines for detection, prevention, and risk reduction. The Panel recommends that all patients with colorectal cancer be screened for Lynch syndrome, which occurs in 1 of every 35 patients and is the most common form of hereditary colorectal cancer. Such screening could be universal so that all tumors are genetically tested, or screening could be restricted to patients under the age of 70 and those aged 70 and older who meet clinical criteria.

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

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e17119 ◽

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]

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