Investigation of promoter methylation of FSCN1 gene and FSCN1 protein expression in differentiated thyroid carcinomas.

FSCN1 gene encodes an actin-bundling protein, FSCN1, which is involved in formation of actin-based structures that contribute to cell migration. High levels of FSCN1 expression is observed in cells with extended membranes and protrusions. Moreover, up-regulation of FSCN1 has been reported in several epithelial carcinomas. Therefore, FSCN1 is thought to play a role in cell movement and invasion. However, the mechanism behind FSCN1 up-regulation is not known. We investigated the expression of FSCN1 using immunohistochemistry. Methylation-specific PCR was adopted to analyze the methylation status of FSCN1 promoter as a potential regulatory mechanism in FSCN1 expression. The samples included papillary thyroid carcinoma, follicular thyroid carcinoma and goiter samples (controls). Methylation of FSCN1 promoter was observed in 50% of follicular, 48.6% of papillary and 60% of controls. The promoter was unmethylated in 16.7% of follicular samples, 5.7% of papillary samples and 26.7% of controls. In the remaining 33.3% of follicular and 45.7% of papillary samples as well as 13.3% of controls, both methylated and unmethylated alleles were amplified, a condition referred to as semi-methylation. The results showed that FSCN1 promoter was significantly hypomethylated in papillary cases while the methylation status was not significantly altered in follicular cases. On the other hand, FSCN1 was expressed in only nine papillary samples. Regarding protein expression and methylation status, we suggest that hypomethylation of FSCN1 promoter in papillary thyroid carcinoma does not lead to overexpression of FSCN1 and that there might be other regulatory mechanisms involved in FSCN1 up-regulation.