FRA-1 protein overexpression is a feature of hyperplastic and neoplastic breast disorders.
BACKGROUND
Fos-related antigen 1 (FRA-1) is an immediate early gene encoding a member of AP-1 family of transcription factors involved in cell proliferation, differentiation, apoptosis, and other biological processes. fra-1 gene overexpression has an important role in the process of cellular transformation, and our previous studies suggest FRA-1 protein detection as a useful tool for the diagnosis of thyroid neoplasias. Here we investigate the expression of the FRA-1 protein in benign and malignant breast tissues by immunohistochemistry, Western blot, RT-PCR and qPCR analysis, to evaluate its possible help in the diagnosis and prognosis of breast neoplastic diseases.


METHODS
We investigate the expression of the FRA-1 protein in 70 breast carcinomas and 30 benign breast diseases by immunohistochemistry, Western blot, RT-PCR and qPCR analysis.


RESULTS
FRA-1 protein was present in all of the carcinoma samples with an intense staining in the nucleus. Positive staining was also found in most of fibroadenomas, but in this case the staining was present both in the nucleus and cytoplasm, and the number of positive cells was lower than in carcinomas. Similar results were obtained from the analysis of breast hyperplasias, with no differences in FRA-1 expression level between typical and atypical breast lesions; however the FRA-1 protein localization is mainly nuclear in the atypical hyperplasias. In situ breast carcinomas showed a pattern of FRA-1 protein expression very similar to that observed in atypical hyperplasias. Conversely, no FRA-1 protein was detectable in 6 normal breast tissue samples used as controls. RT-PCR and qPCR analysis confirmed these results. Similar results were obtained analysing FRA-1 expression in fine needle aspiration biopsy (FNAB) samples.


CONCLUSIONS
The data shown here suggest that FRA-1 expression, including its intracellular localization, may be considered a useful marker for hyperplastic and neoplastic proliferative breast disorders.
Chiappetta
Gennaro
G
Istituto Nazionale dei Tumori di Napoli Fondazione Senatore Pascale, Naples, Italy. chiappetta.osd@fondazionepascale.it <chiappetta.osd@fondazionepascale.it>
Ferraro
Angelo
A
Botti
Gerardo
G
Monaco
Mario
M
Pasquinelli
Rosa
R
Vuttariello
Emilia
E
Arnaldi
Liliane
L
Di Bonito
Maurizio
M
D'Aiuto
Giuseppe
G
Pierantoni
Giovanna Maria
GM
Fusco
Alfredo
A
D044963:Biopsy, Fine-Needle; D001941:Breast Diseases / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D006965:Hyperplasia / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D000099169:Fos-Related Antigen 1
D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D000099169:Fos-Related Antigen 1