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Microsatellite Instability Occurs in a Subset of Follicular Thyroid Cancers.
Thyroid : Official Journal of the American Thyroid Association 2019 Februrary 13
BACKGROUND: Inactivation of DNA mismatch repair (MMR) and the resulting microsatellite instability (MSI) are frequently observed in endometrial, stomach and colorectal cancers as well as more rarely in other solid tumor types. The prevalence of MSI in thyroid cancer has not been explored in-depth, although recent studies utilizing data from large cancer sequencing efforts such as The Cancer Genome Atlas indicate MSI is absent or at least very rare in the most common and most well-studied histologic subtype, papillary carcinoma. In this study, we aim to determine the prevalence of MSI in thyroid cancer by using a large series comprising all major histological subtypes.
METHODS: we screened a total of 485 thyroid cancer patients for MSI/MMR deficiency, including all major histologic subtypes (195 papillary, 156 follicular (FTC), 50 anaplastic, 65 medullary, and 17 poorly differentiated thyroid carcinomas), by using a combination of PCR-based detection, immunohistochemistry, and next generation sequencing.
RESULTS: A total of four tumors were MSI-high (MSI-H) and had loss of MMR protein expression, all of which were from FTC patients. Whole exome sequencing was performed on two MSI-H FTCs and revealed a hemizygous loss of function mutation in MSH2 in one tumor.
CONCLUSIONS: Based on these data, we estimate that the overall prevalence of MSI in FTC is 2.5%, and MSI is either entirely absent or rare in other histology subtypes of thyroid carcinoma. These findings highlight the importance of testing for MSI in follicular thyroid cancer. .
METHODS: we screened a total of 485 thyroid cancer patients for MSI/MMR deficiency, including all major histologic subtypes (195 papillary, 156 follicular (FTC), 50 anaplastic, 65 medullary, and 17 poorly differentiated thyroid carcinomas), by using a combination of PCR-based detection, immunohistochemistry, and next generation sequencing.
RESULTS: A total of four tumors were MSI-high (MSI-H) and had loss of MMR protein expression, all of which were from FTC patients. Whole exome sequencing was performed on two MSI-H FTCs and revealed a hemizygous loss of function mutation in MSH2 in one tumor.
CONCLUSIONS: Based on these data, we estimate that the overall prevalence of MSI in FTC is 2.5%, and MSI is either entirely absent or rare in other histology subtypes of thyroid carcinoma. These findings highlight the importance of testing for MSI in follicular thyroid cancer. .
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