Reduced Expression of Fanconi Anemia Complementation Group F (FANCF) 4 Is Associated with an Aggressive Phenotype and Shortened Survivial in Breast Cancer
EA Slodkowska, AB Boguniewicz, CE Sheehan, JS Ross. Albany Medical College, Albany, NY
Background: The Fanconi anemia complex is composed of multiple members including the BRCA2 gene and functions to maintains DNA stability. Germline mutations in Fanconi genes are associated with cancer suceptibility. The expression of FANCF4 is regulated by promoter gene methylation and has been linked to sporadic cancer development. To date, FANCF 4 expression has not been studied as a potential prognostic factor in breast cancer.
Design: Formalin-fixed, paraffin-embedded tissue sections from 163 cases of invasive mammary carcinoma (123 ductal carcinomas (IDC) and 40 lobular carcinomas (ILC) were immunostained by automated methods (Ventana Medical Systems Inc., Tucson, AZ) using rabbit polyclonal FANCF (LifeSpan Biosciences, Seattle, WA). Cytoplasmic immunoreactivity was semiquantitatively scored based on staining intensity (weak, moderate, intense) and distribution (focal, regional, diffuse) and the results were correlated with morphologic and prognostic variables. Reduced FANCF 4 expression was defined as complete, regional or focal loss of tumor immunoreactivity compared with normal epithelial expression.
Results: For all invasive tumors, reduced cytoplasmic FANCF 4 protein expression was observed in 88/163 (54%) invasive tumors. Decreased FANCF 4 expression correlated with ER negative status [66% ER negative tumors vs 47% ER positive tumors, p=0.02], PR negative status [64% PR negative tumors vs 45% PR positive tumors, p=0.02], and shortened overall survival [60% expired vs 43% alive, p=0.03]. The association of reduced FANCF expression with advanced tumor stage reached near significance [68% advanced stage vs 50% early stage, p=0.08] for all tumors, but was significant for the ILC subgroup [90% advanced stage vs 53% early stage, p=0.03]. On multivariate analysis, young age at diagnosis, advanced stage, node positive status, HER2 positive status and disease recurrence predicted reduced overall survival.
Conclusions: Reduced FANCF 4 expression in invasive breast cancer is associated with an aggressive phenotype and shortened overall survival. Further study of the prognostic significance of FANCF 4 expression in breast cancer appears warranted.
Monday, March 9, 2009 1:00 PM
Poster Session II # 35, Monday Afternoon