Clinicopathological Significance of Overall Frequency of Allelic Loss (OFAL) in Lesions Derived from Thyroid Follicular Cell

Background Loss of heterozygosity (LOH) and microsatellite instability (MSI) are frequent molecular events in thyroid tumor etiopathogenesis occurring in several chromosomal critical areas, including 3p12–25.3, 7q21–31, 10q22–24, and 15q11–13, with loci of tumor suppressor genes. Objective We evalua...

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Published in:Molecular diagnosis & therapy 2019-06, Vol.23 (3), p.369-382
Main Authors: Migdalska-Sęk, Monika, Czarnecka, Karolina H., Kusiński, Michał, Pastuszak-Lewandoska, Dorota, Nawrot, Ewa, Kuzdak, Krzysztof, Brzeziańska-Lasota, Ewa
Format: Article
Language:English
Subjects:
Adenoma
Biomarkers
Biomedical and Life Sciences
Biomedicine
Cancer Research
Chromosome 15
Chromosomes
Deoxyribonucleic acid
DNA
Genetic markers
Genetic testing
Goiter
Heterozygosity
Human Genetics
Laboratory Medicine
Lesions
Loss of heterozygosity
Metastasis
Microsatellite instability
Microsatellites
Molecular Medicine
Original
Original Research Article
Papillary thyroid carcinoma
Pharmacotherapy
Regions
Surgery
Thyrocytes
Thyroid
Thyroid cancer
Tumor suppressor genes
Tumorigenesis
Tumors
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Summary:Background Loss of heterozygosity (LOH) and microsatellite instability (MSI) are frequent molecular events in thyroid tumor etiopathogenesis occurring in several chromosomal critical areas, including 3p12–25.3, 7q21–31, 10q22–24, and 15q11–13, with loci of tumor suppressor genes. Objective We evaluated the usefulness of LOH/MSI as a diagnostic/prognostic biomarker in lesions derived from thyroid follicular cells: follicular thyroid carcinoma (FTC); follicular adenoma (FA), papillary thyroid carcinoma (PTC), and nodular goiter (NG). Methods We performed allelotyping (GeneMapper Software v. 4.0.) of ten microsatellite markers linked to the 1p31.2, 3p21.3, 3p24.2, 9p21.3, 11p15.5, and 16q22.1 region on DNA from 93 primary thyroid lesions then evaluated the LOH/MSI frequency and overall frequency of allelic loss (OFAL). Results We found regions with significantly increased frequency of LOH/MSI for specific histotypes: the 3p24.2 region for FA and 1p31.2 for FTC. LOH/MSI in 3p21.3 was significantly elevated in PTC and FTC. LOH/MSI in 3p21.3 was increased for small size tumors (T1a + T1b), tumors with no regional lymph node involvement (N0 + Nx), American Joint Committee on Cancer (AJCC) stage I tumors, and tumor diameter (Td)  30 mm. OFAL values were significantly higher in younger patients (
ISSN:1177-1062
1179-2000
DOI:10.1007/s40291-019-00387-0