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Int J Clin Exp Pathol 2010;3(5):482-491

Original Article
Association of the promoter methylation and protein expression of fragile histidine triad
(FHIT) gene with the progression of differentiated thyroid carcinoma

De-Tao Yin, Lin Wang, Jianrui Sun, Fengyan Yin, Qingtao Yan, Rulong Shen, Gang He, Jian-Xin Gao

Department of General Surgery, Department of Information, and Department of Neurosurgery, the First Affiliated Hospital of Zhengzhou
University, Zhengzhou, 450052, P. R. China, a visiting scholar and research fellow at Dept. of Pathology, OSU.
Department of Pathology and Comprehensive Cancer Center, Ohio State University, Columbus, OH 43210, USA

Received April 27, 2010, accepted May 18, 2010, available online: May 25, 2010

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 the inactivation of FHIT - possibly leading to subsequent carcinogenesis and
progression of DTC. (IJCEP1004010).

Key words: Fragile histidine triad; differentiated thyroid carcinoma; methylation; carcinogenesis; tumor progression

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Address all correspondence to:
De-Tao Yin, M.D.
Department of General Surgery
The First Affiliated Hospital of Zhengzhou University
Zhengzhou, 450052
P.R. China


Jian-Xin Gao, M.D., Ph.D.
Department of Pathology
Ohio State University Medical Center
129 Hamilton Hall
1645 Neil Avenue
Columbus, OH 43210