title: Association of the promoter methylation and protein expression of Fragile Histidine Triad (FHIT) gene with the progression of differentiated thyroid carcinoma.
abstract: The role of aberrant methylation of fragile histidine triad (FHIT) promoters in the differentiated thyroid carcinoma (DTC) is not yet clear. Therefore, we investigated the association of the status of FHIT promoter methylation and FHIT protein expression with the clinicopathological progression of DTC, using PCR-based methylation assay and immunohistochemical technique. While no FHIT gene promoter methylation was observed in the matched non-cancerous epithelium (NCE) specimens, 24.6% of DTC samples demonstrated methylation in the FHIT promoter region. The protein expression of FHIT in NCE and DTC was 100.0% and 41.5% (P<0.01), respectively. There was a negative correlation between promoter methylation and protein expression of FHIT gene (P<0.05). Additionally, the methylation status appeared to be significantly associated with the pathological grade, tumor TNM stage, and lymph node metastasis (P<0.05), and FHIT proteins were weakly expressed in only about 20% of DTC with grade II pathological changes, TNM stage III/IV, or lymph node metastasis. Finally, the gender and tumor classification but not age marginally affected the promoter methylation and protein expression of FHIT. Our results suggest that methylation of the promoter region may play a key role in inactivation of FHIT - possibly leading to subsequent carcinogenesis and progression of DTC.
authors.affiliation: Department of General Surgery, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, P. R. China.
authors.forename: De-Tao
authors.initials: DT
authors.lastname: Yin
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.forename: Jianrui
authors.initials: J
authors.lastname: Sun
authors.forename: Fengyan
authors.initials: F
authors.lastname: Yin
authors.forename: Qingtao
authors.initials: Q
authors.lastname: Yan
authors.forename: Rulong
authors.initials: R
authors.lastname: Shen
authors.forename: Gang
authors.initials: G
authors.lastname: He
authors.forename: Jian-Xin
authors.initials: JX
authors.lastname: Gao
mesh_terms: D017766:Acid Anhydride Hydrolases / Q000096:biosynthesis* / Q000235:genetics; D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000293:Adolescent; D000328:Adult; D000368:Aged; D019175:DNA Methylation / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic / Q000235:genetics*; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology; D055815:Young Adult; D000099170:Bis(5'-adenosyl)triphosphatase
chemical_list: D017766:Acid Anhydride Hydrolases; D009363:Neoplasm Proteins; D000099170:Bis(5'-adenosyl)triphosphatase