An association of a simultaneous nuclear and cytoplasmic localization of Fra-1 with breast malignancy

BACKGROUND: Overexpression of Fra-1 in fibroblasts causes anchorage-independent cell growth and oncogenic transformation. A high level of Fra-1 expression is found in various tumors and tumorigenic cell lines, suggesting that Fra-1 may be involved in malignant progression. This study aimed to investigate the significance of Fra-1 expression in breast carcinogenesis. METHODS: The expression of Fra-1 was investigated by immunohistochemistry in neoplastic breast diseases ranging from benign fibroadenoma to very aggressive undifferentiated carcinoma. The correlations of Fra-1 expression with other indicators of breast carcinoma prognosis (ER, PR and ErbB2 receptors) were analyzed. RESULTS: All neoplastic breast tissues, either benign or malignant breast tissues, were nuclear immunoreactive for Fra-1-recognizing antibody. The pattern of Fra-1 expression by benign neoplastic cells was predominantly nuclear. However, the nuclear/cytoplasmic concomitant immunoreactivity was observed in all types of breast carcinomas. A clear shift in Fra-1 immunoreactivity, from an exclusively nuclear to a simultaneous nuclear and cytoplasmic localization was noticed in ~90% of breast carcinomas. CONCLUSION: The overall expression, pattern and intensity of Fra-1 proteins were correlated with breast oncogenesis. Overexpression of Fra-1, leading to a persistent high cytoplasmic accumulation, may play a role in the process of breast carcinogenesis.