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Tumor analysis: Test all MSI-high patients for Lynch Syndrome


Key clinical point: All MSI-high patients should be tested for LS regardless of cancer type or family history.

Major finding: LS was present in 16.3% of MSI-high tumors vs. 1.9% and 0.3% of MSI-indeterminate and stable tumors, respectively.

Study details: An analysis of 15,045 tumor samples.

Disclosures: This study was funded by Romeo Milio Lynch Syndrome Foundation, the Marie-Josee and Henry R. Kravis Center for Molecular Oncology, the Robert and Kate Niehaus Center for Inherited Cancer Genomics, the Fieldstone Family Fund, Stand Up to Cancer Colorectal Cancer Dream Team Translational Research Grant, and the NIH/NCI Cancer Center Support Grant. Dr. Stadler reported consulting or advisory roles on the part of an immediate family member for Allergan, Genentech/Roche, Regeneron, Optos, and Adverum.

Source: Schwark A et al. ASCO 2018 LBA 1509.



High frequency microsatellite instability (MSI-high) predicts Lynch Syndrome– and does so across more tumor types than previously expected, according to “absolutely practice changing” findings from a prospective analysis of more than 15,000 tumor samples.

Sharon Worcester/MDedge News

Dr. Zsofia K. Stadler

“The impact of these findings cannot be understated,” ASCO expert Shannon N. Westin, MD, said during a discussion of the findings presented by Zsofia K. Stadler, MD, at a press briefing at the annual meeting of the American Society of Clinical Oncology.

Lynch Syndrome (LS), an autosomal dominant inherited cancer predisposition syndrome caused by germline mutation in the DNA mismatch repair genes, is responsible for about 3% of colorectal and endometrial cancers; universal testing for tumor markers of LS is recommended in all patients with these types of cancers, said Dr. Stadler, director of the Clinical Genetics Service at Memorial Sloan Kettering Cancer Center, New York.

“This is usually done either via MSI analysis or immunohistochemical staining for the DNA mismatch repair proteins,” she said, noting that genetic testing and counseling is recommended in patients with tumors suggestive of LS, and increased surveillance and/or risk-reducing surgery is recommended in those recognized as having LS.

MSI-high is a hallmark of LS-associated cancers and has recently been implicated as a marker for response to immunotherapy. This has led to increased MSI testing in metastatic cancer regardless of cancer type.

However, the prevalence of germline mutations in the DNA mismatch repair genes diagnostic of LS across all MSI-high tumors is unknown, she said.

In 15,045 tumor samples across more than 50 cancer types, germline mutations were analyzed across tumor types and according to MSI status.


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