Is Fascin-1 an additional prognostic marker for invasive breast carcinoma?
New York University Medical Center, New York, NY, United States
AIM: Fascin-1, an actin bundling protein, plays a pivotal role in cell adhesion and mobility. Over-expression of Fascin-1 in epithelial cells correlates with disorganization of adherens junction and decreased cell-cell attachment. Fascin-1 is overexpressed/ upregulated in ER-/PR- breast carcinomas and in Her2/neu+ human breast cancer cell lines, suggesting an association with a more aggressive behavior and a poorer prognosis. In order to further understand the function of Fascin-1 in breast carcinoma, we investigated the correlation of Fascin-1 expression with estrogen receptors (ER), progesterone receptors (PR), Her2/neu, p53, and p27 in invasive breast carcinomas. METHODS: Paraffin-embedded sections of invasive breast carcinomas with prognostic marker studies were retrieved from NYU Medical Center computerized archives and divided into 4 groups: ER+/PR-(N=10), ER-/PR+ (N=10), ER+/PR+ (N=10), and ER-/PR- (N=20). Immunohistochemistry was performed using monoclonal antibodies for Fascin-1 (Neomarkers), ER, PR, Her2/neu, p53, and p27 (Ventana). Only cases with more than 90% ER/PR positive cells or unequivocally positive expression of Her2/neu (+++) were selected. Fascin-1 expression, independantly recorded by three observers, was scored as positive if diffuse staining was observed in more than 50% of the cells, borderline if present in 5 to 50% of the cells, negative if present in less than 5% of the cells. RESULTS:All cases with ER+/PR-, ER-/PR+, or ER+/PR+ did not show any immunohistochemically detectable Fascin-1 expression. Fascin-1 was positive in 8 of 20 ER-/PR- cases(40%). The reversal association was confirmed with double immunohistochemical staining of Fascin-1 with ER or PR. However, the remaining 12 ER-/PR- invasive breast carcinomas(60%) did not express Fascin-1. There was no borderline result. Her2/neu, p53, and p27 did not affect Fascin-1 expression in ER-/PR- cases. Interestingly, normal acinar cells were diffusely positive for Fascin-1. Conclusion: ER or PR down-regulates Fascin-1 expression in breast carcinomas, while absence of both up-regulates its expression in a subset of breast carcinomas. However 60% of ER-/PR- cases lack Fascin-1 expression, as opposed to a previous smaller scale study. There is no evidence that Her2/neu over-expression increases Fascin-1 expression by immunohistochemistry, in contrast to studies on human breast cancer cell lines. These findings tend to indicate that there are other pathways involving the regulation of Fascin-1 expression and therefore its prognostic role needs to be further defined.
Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Nice, France; February 7 - 10, 2004; in poster session 797 (Manifestations of cancer).