fra-1 gene overexpression has been shown to represent a general event in thyroid cell transformation in vitro and in vivo. Moreover, inhibition of
FRA-1 protein synthesis by stable transfection with a fra-1 antisense construct significantly reduces the malignant phenotype of the transformed thyroid cells, indicating a pivotal role of the fra-1 gene product in the process of cellular transformation. In the attempt to define the potential use of
FRA-1 protein detection in the diagnosis of
thyroid diseases, we analyzed Fra-1 expression by a combination of immunohistochemistry and reverse transcription-PCR (RT-PCR) assay in 174 samples of
thyroid nodules (22 nodular
hyperplasias, 102
follicular adenomas, 34
papillary carcinomas, 12 follicular
carcinomas, and 4
anaplastic carcinomas) representative of the spectrum of thyroid
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 cytoplasm. 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. Similar results were obtained from the analysis of thyroid
goiters; however, the number of positive cases is lower than
adenomas (8 of 22; 36%); moreover, the staining was not observed in all of the cells. Conversely, no
FRA-1 protein was detectable in 12 normal thyroid tissue samples used as controls. RT-PCR analysis confirmed a higher fra-1 expression in papillary and follicular
carcinomas compared with
goiters and
adenomas. fra-1 expression was also analyzed on 10 fine needle aspiration biopsy (FNAB) samples by RT-PCR. fra-1-specific
mRNA was detected in seven of the eight FNABs corresponding to
thyroid nodules that were eventually diagnosed as
adenomas (three of four) and
carcinomas (four of four) after surgery. Conversely, no fra-1 gene expression was observed in two FNABs derived from normal thyroid. Further studies are required before suggesting
FRA-1 protein detection as a useful tool for the diagnosis of hyperplastic and neoplastic disorders of the thyroid gland.