Fra-1 Expression In In Situ And Invasive Ductal Breast Carcinomas: Association With Worse Prognosis In Invasive Basaloid Tumors

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. 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. Objective: Evaluate the significance of Fra-1 expression in breast carcinogenesis and its possible help in sub typing and prognosis of breast carcinomas. Methods: Fra-1 expression was investigated by immunohistochemistry in a Tissue Microarray composed by neoplastic breast tissue from 85 in situ breast carcinomas lesions and 769 invasive ductal carcinomas NOS (IDC), ranging from early stage T1 N0M0 to very aggressive metastatic disease (TxN1-3M1). Positive and negative controls were present in each reaction. Nuclear staining were considered positive. Correlations of Fra-1 expression with other indicators of breast carcinoma prognosis (ER, PR TNM, survival) were analyzed. Results: IDC showed 22.8 % of positivity while in situ lesions maintained a 42.2% of reactive cases. In IDC samples, Fra-1 expression correlated with markers of invasiveness, as Node status, histological grade ( P = 0.005 and 0.001, chi-square test) and marginally with presence of metastasis ( P = 0.07). Fra-1 was also associated to Cytokeratin (CK) 14 ( P = 0.043) and marginally to CK18 and her-2 status ( P =0.063 and 0.05), and indirectly to estrogen receptor ( P = 0.01). When we select basaloid (CK6 positive, ER negative) cases Fra-1 was associated to worse prognosis ( P = 0. 013 - Log Rank test). Conclusions: The data shown here suggest that Fra-1 expression is progressively lost during cancer progression from DCIS to IDC. Fra-1 expression in IDC basaloid tumors confers a worse prognosis. Supported by FAPESP no 04/04607-8. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 2129.