LQPB220X - CMLE - THE IMPORTANCE OF THE LABORATORY PROFESSIONAL IN THE DIAGNOSIS OF LYNCH SYNDROME-LQPB220X

LQPB220X - Educational Activity

Pdf Summary

The document provides an in-depth analysis of Lynch syndrome, a genetic disorder linked to a high risk of colorectal and endometrial cancers. The text is authored by Megan Sweeney, a Medical Laboratory Scientist specializing in Molecular Diagnostics. The document is intended for participants in the ASCP LabQ 2022 Phlebotomy Bonus Exercise, aiming to enhance their understanding of Lynch syndrome diagnosis and inheritance patterns.<br /><br />Lynch syndrome is an autosomal dominant genetic condition, indicating a 50% chance of passing the mutation to offspring. It primarily involves deficiencies in the mismatch repair (MMR) system, with key genes including MLH1, MSH2, MSH6, and PMS2. The MMR system corrects DNA replication errors; mutations here lead to an accumulation of errors, increasing cancer risk, particularly in the colon and uterus.<br /><br />A case study is presented involving a 35-year-old woman with symptoms suggesting colorectal cancer. Tests including stool occult blood, blood markers, and a CT scan led to a colonoscopy that identified colorectal adenocarcinoma. Immunohistochemistry (IHC) revealed a possible Lynch syndrome diagnosis due to absent MLH1 and PMS2 protein expressions.<br /><br />The history of Lynch syndrome investigation dates back to the early 20th century, with significant contributions from Dr. Henry T. Lynch. The disease was initially referred to as hereditary non-polyposis colorectal cancer (HNPCC).<br /><br />In addition to IHC, microsatellite instability (MSI) testing is discussed as an essential tool for diagnosing MMR deficiency. MSI testing involves comparing DNA from tumor and normal tissues to identify instability. An MSI-High (MSI-H) result indicates significant instability, necessitating further testing via next-generation sequencing (NGS). NGS helps pinpoint mutations in MMR genes and excludes other possible causes like epigenetic changes.<br /><br />The document concludes with the acknowledgment of the improved diagnosis and management of Lynch syndrome through molecular diagnostics, recommending all colorectal and endometrial cancers be tested for MMR deficiency. It emphasizes the importance of laboratory professionals in accurately identifying and managing this syndrome, thereby enhancing patient outcomes through early detection and appropriate clinical management.

Keywords

Lynch syndrome

colorectal cancer

endometrial cancer

genetic disorder

mismatch repair

MLH1

MSH2

MSI testing

next-generation sequencing

Megan Sweeney