Microsatellite Instability is Present in a Subset of Follicular Thyroid Carcinomas
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Date
2018-05
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The Ohio State University
Abstract
Microsatellite instability (MSI) is a term used to describe the somatic addition or loss of bases within repetitive DNA sequences called microsatellites and is characteristic of certain cancer types- specifically endometrial cancer (~30% of patients), colorectal cancer (~15% of patients) and stomach cancer (~15% of patients). MSI can have prognostic and predictive implications, and recently MSI was shown to be a predictor of response to anti-Programmed Death Ligand 1 (PD-L1) immunotherapy, which has substantially improved outcome in several cancers. Although the thyroid is one of the most common cancer sites, the prevalence of MSI in thyroid cancer has not been accurately defined. Previous studies on MSI in thyroid cancer have focused almost exclusively on the most common histological subtype, papillary thyroid carcinoma (PTC). Herein we have screened for MSI in a large set of thyroid cancer samples representing all major histologic subtypes. Defining MSI status has been standardized by polymerase chain reaction (PCR) of five specific microsatellites, and tumors are considered MSI-positive (MSI+) if at least two of the five markers show MSI. Using PCR, we screened a total of 191 thyroid cancer cases including: 122 PTC, 35 follicular thyroid carcinomas (FTC), 20 medullary thyroid carcinomas, and 14 anaplastic thyroid carcinomas. MSI was observed in 5% of FTC cases by PCR and validated with immunohistochemistry staining of the MMR proteins. A separate cohort of 184 thyroid carcinoma cases of various histologies was screen for MSI using a more recent technique based on next-generation sequencing (NGS). A total of 10 cases were predicted to be MSI by this method, three of which were FTCs. The presence of MSI in FTC, even in a small percentage of cases, could have important clinical implications. Screening for MSI is already performed for newly diagnosed colorectal cancers in Ohio hospitals, as part of the Ohio Colorectal Cancer Prevention Initiative. FTC patients could likewise be screened for MSI upon diagnosis, and patients shown to be MSI positive could be treated with the remarkable PD-1 immunotherapy. Together, this project will provide a comprehensive evaluation of MSI in thyroid cancer.
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Keywords
Microsatellite Instability, Mismatch Repair, Cancer, Thyroid Cancer