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


METHODS
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.


METHODS
A university tertiary care center and regional veterans' hospital.


METHODS
Fifty-five patients undergoing partial or total thyroidectomies for various indications (PTC, HT, or goiter).


METHODS
Pathology specimens were analyzed by laser capture microdissection and PCR for hOGG1.


METHODS
The presence of hOGG1 in all thyroid specimens.


RESULTS
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%).


CONCLUSIONS
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.
Royer
Mark C
MC
Department of Otolaryngology-Head and Neck Surgery, Indiana University School of Medicine, Indianapolis, USA.
Zhang
Haihong
H
Fan
Chun-Yang
CY
Kokoska
Mimi S
MS
D002291:Carcinoma, Papillary / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D045647:DNA Glycosylases / Q000235:genetics*; D006042:Goiter / Q000235:genetics / Q000473:pathology / Q000601:surgery; D050031:Hashimoto Disease / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D006801:Humans; D019656:Loss of Heterozygosity; D042282:Microdissection; D018895:Microsatellite Repeats; D016133:Polymerase Chain Reaction; D013961:Thyroid Gland / Q000473:pathology; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D013965:Thyroidectomy
D045647:DNA Glycosylases; C479058:oxoguanine glycosylase 1, human