Genetic alterations in papillary thyroid carcinoma and hashimoto thyroiditis: An analysis of hOGG1 loss of heterozygosity.

To determine the relationship between hOGG1 loss of heterozygosity (LOH), Hashimoto thyroiditis (HT), and papillary thyroid cancer (PTC). Hashimoto thyroiditis is an autoimmune mediated chronic inflammatory disease previously shown to coexist with papillary PTC. To further define the relationship between HT and PTC, we report an analysis of hOGG1, a major repair gene for free radical-induced oxidative DNA damages, in thyroidectomy specimens. Tissue samples from 20 cases of PTC, 20 cases of HT, and 15 cases of benign goiter were included in this study. Samples of DNA collected from laser-capture microdissection of thyroidectomy specimens were analyzed for hOGG1 LOH by polymerase chain reaction (PCR) amplification using 5 fluorescent-labeled microsatellite markers followed by fragment analysis. A university tertiary care center and regional veterans' hospital. Fifty-five patients undergoing partial or total thyroidectomies for various indications (PTC, HT, or goiter). Pathology specimens were analyzed by laser capture microdissection and PCR for hOGG1. The presence of hOGG1 in all thyroid specimens. Amplification by PCR was successful for all 5 markers in 18 cases of PTC, 15 cases of HT, and 12 cases of benign thyroid. Among these samples, hOGG1 LOH was found in 17 of 18 PTC specimens (94%), 11 of 15 HT specimens (73%), and 1 of 12 benign goiter specimens (8%). hOGG1 LOH is strongly associated with PTC and HT but not with benign thyroid. We hypothesize that thyroid follicular epithelia accumulate aberrant genetic changes in long-standing HT, which may represent a precursor lesion of PTC.