FRA-1 expression in hyperplastic and neoplastic thyroid diseases

fra-1 gene overexpression has been shown to represent a general event in th yroid cell transformation irt vitro and in vivo. Moreover, inhibition of FR A-1 protein synthesis by stable transfection with a fra-1 antisense constru ct significantly reduces the malignant phenotype of the transformed thyroid cells, indicating a pivotal role of the fm-l gene product in the process o f cellular transformation, In the attempt to define the potential use of FR A-1 protein detection in the diagnosis of thyroid diseases, we analyzed Fra -1 expression by a combination of immunohistochemistry and reverse transcri ption-PCR (RT-PCR) assay in 174 samples of thyroid nodules (22 nodular hype rplasias, 102 follicular adenomas, 34 papillary carcinomas, 12 follicular c arcinomas, and 4 anaplastic carcinomas) representative of the spectrum of t hyroid tumor pathology. FRA-1 protein was abundant in all of the carcinoma samples (50/50, 100%), with an intense staining in the nucleus and the cyto plasm, Positive staining was also found in most of the adenomas (90 of 102; 88%), but in this case, the staining was restricted to the nucleus, Simila r results were obtained from the analysis of thyroid goiters; however, the number of positive cases Is lower than adenomas (8 of 22; 36%); moreover, t he staining was not observed in all of the cells. Conversely, no FRA-1 prot ein was detectable in 12 normal thyroid tissue samples used as controls. RT -PCR analysis confirmed a higher fra-1 expression in papillary and follicul ar carcinomas compared with goiters and adenomas, fra-1 expression was also analyzed on 10 fine needle aspiration biopsy (FNAB) samples ba RT-PCR, fm- l-specific mRNA was detected in seven of the eight FNABs corresponding to t hyroid nodules that were eventually diagnosed as adenomas (three of four) a nd carcinomas (four of four) after surgery. Conversely, no fra-1 gene expre ssion was observed in two FNABs derived from normal thyroid, Further studie s are required before suggesting FRA-1 protein detection as a useful tool f or the diagnosis of hyperplastic and neoplastic disorders of the thyroid gl and.