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).