Fascin expression predicts an aggressive clinical course in patients with advanced breast cancer

Abstract

Fascin is an actin cross-linking protein, which regulates actin dynamics and filopodia or spike formation, as well as the epithelial-mesenchymal transition, and has been implicated in cell motility. Although, fascin is pivotal in mediating the aggressive behaviour of various types of cancer, its prognostic significance according to tumour stage has yet to be evaluated. Therefore, the present study investigated fascin expression in 194 patients diagnosed with invasive ductal carcinoma of the breast between 2000 and 2005. Fascin protein expression levels were evaluated by immunostaining on a tissue microarray, and the association between fascin expression and various clinicopathological parameters was analysed. Fascin expression was significantly correlated with various clinicopathological parameters, including high histological grade, tumour necrosis, resistance to adjuvant therapy, high expression of p53 and Ki-67 and specific therapeutic markers (oestrogen and progesterone receptor negativity; all P<0.05). Furthermore, univariate and multivariate analyses identified a significant association between fascin expression, and poor disease-free and overall survival, in late-stage breast cancer (all P<0.05). Therefore, fascin may be crucial in predicting aggressive tumour behaviour, particularly in patients with advanced-stage disease that has acquired the properties of migration and invasion.

Keywords: fascin-1 protein; human breast cancer; invasive ductal carcinoma; prognosis.

Figure 1.

Representative microphotographs revealing (A) negative, (B) weak, (C) moderate and (D) strong intensity fascin expression using immunohistochemical staining (original magnification ×200).

Figure 2.

ROC curve for determination of the optimal cut-off value for fascin expression correlated with overall survival rate in patients with invasive ductal carcinoma of the breast (area under the ROC, 0.572). ROC, receiver operating curve.

Figure 3.

Fascin expression is more frequently observed in triple-negative cases of breast cancer compared with other subtypes (P<0.001). HER2, human epithelial growth factor receptor 2.

Figure 4.

Fascin expression is correlated with poor disease-free and overall survival rates in patients with invasive duct carcinoma of the breast. (A) Disease-free and (B) overall survival curves derived using the Kaplan-Meier method, demonstrating significant correlation with fascin expression. Disease-free survival, P=0.045; overall survival, P=0.004.

Figure 5.

Fascin expression is correlated with disease-free and overall survival rates, according to T3, nodal metastasis and AJCC stage III in invasive duct carcinoma of the breast. (A) Disease-free and (B) overall survival curves derived using the Kaplan-Meier method, demonstrating significant correlation with fascin expression according to T3, nodal metastasis and AJCC stage III advanced breast cancer. Disease-free survival, P=0.001, 0.009 and 0.007; overall survival P=0.013, 0.001 and 0.004, respectively. AJCC, American Joint Committee on Cancer.