LQCL2213 - CMLE - THE IMPORTANCE OF THE LABORATORY PROFESSIONAL IN THE DIAGNOSIS OF LYNCH SYNDROME-THE IMPORTANCE OF THE LABORATORY PROFESSIONAL IN THE DIAGNOSIS OF LYNCH SYNDROME

THE IMPORTANCE OF THE LABORATORY PROFESSIONAL IN THE DIAGNOSIS OF LYNCH SYNDROME

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The provided document is a comprehensive study on molecular diagnostics related to Lynch syndrome, authored by Megan Sweeney, MLS(ASCP) MB, at Circulogene Theranostics in Pensacola, Florida, in 2022. The key elements encompass learning objectives, a historical case, and discussions on the importance of laboratory professionals in diagnosing Lynch syndrome.<br /><br />### Learning Objectives:<br />Participants will:<br />- Explain Lynch syndrome inheritance patterns.<br />- Differentiate MMR proteins based on their roles.<br />- Illustrate MSI-S and MSI-H capillary electrophoresis results.<br />- Correlate MSI/IHC results with genes detected via next-generation sequencing.<br />- Describe the clinical utility of IHC and MSI results.<br /><br />### Historical Overview:<br />Lynch syndrome was initially identified in a family suffering from high cancer rates, known as Cancer Family G. Dr. Henry T. Lynch continued studies in the 1960s, identifying the syndrome as an autosomal dominant trait with a 50% likelihood of being inherited. Significant developments in genetic testing now allow for faster and more accurate diagnostic methods.<br /><br />### Diagnostic Techniques:<br />- **Immunohistochemistry (IHC):** Uses labeled antibodies to identify MMR protein expressions in tumor cells.<br />- **Microsatellite Instability Testing (MSI):** PCR-based method detecting changes in microsatellite regions, comparing tumor DNA with normal DNA. Shifts in microsatellite markers classify the DNA as MSI-H (>40% markers shifted) or MSS (stable).<br />- **Next-Generation Sequencing (NGS):** Identifies mutations in MMR and related genes (MLH1, MSH2, PMS2, MSH6). It's efficient and enhances familial screening specificity.<br /><br />### Case History:<br />A 35-year-old woman with chronic constipation and bloating was diagnosed with colorectal adenocarcinoma after undergoing various medical tests. IHC and MSI tests suggested possible Lynch syndrome. Confirmatory NGS revealed a mutation in the MLH1 gene, leading to a Lynch syndrome diagnosis, and subsequent genetic counseling and treatment.<br /><br />### Conclusion:<br />Laboratory diagnostics reveal a higher prevalence of Lynch syndrome mutations, previously underestimated. This enables better health management for patients and their families. Lynch syndrome-associated cancers can be detected early, with improved outcomes through molecular testing and targeted immunotherapies.<br /><br />### Additional Information:<br />Testing guidelines have expanded to routinely screen all colorectal and endometrial cancers for MMR deficiencies. Lynch syndrome's identification through molecular diagnostics provides valuable information for patient prognosis and familial cancer screening, aiming for early detection and better management of associated cancers.

Keywords

Lynch syndrome

molecular diagnostics

MMR proteins

MSI testing

IHC

next-generation sequencing

genetic testing

colorectal adenocarcinoma

familial cancer screening

Megan Sweeney