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

Abstract

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. IntroductionBreast cancer is the most commonly diagnosed neoplasm and the third leading cause of cancer-associated mortality in the United States, with 22.2 mortalities per 100,000 women associated with breast cancer each year. The five-year relative survival rate for breast cancer has gradually increased since the early 1990s and between 2007 and 2011 it was ~89.2%. However, the prognosis of patients with breast cancer is dependent on the disease stage at the time of diagnosis. In particular, the survival rates of patients with localised disease and regional lymph node metastasis at diagnosis are higher than those of patients presenting with distant metastasis (1). A number of studies have established molecular markers, which are associated with distinct histopathological features, the response to adjuvant therapy and/or the clinical outcome of breast cancer (2-7). Furthermore, the following clinicopathological factors are considered to be useful markers for predicting prognosis and identifying therapeutic targets in patients with advanced breast cancer: American Joint Committee on Cancer (AJCC) stage, histological grade, oestrogen receptor (ER) and progesterone receptor (PR) expression, human epithelial growth factor receptor 2 (HER2) amplification, p53 expression and Ki-67 labelling index (2-6). Based on data obtained from molecular or immunohistochemical (IHC) analyses, breast cancer is classified into four major subtypes: Luminal A, luminal B, basal-like and HER2-positive (7). More recently, the luminal B subtype has been subdivided according to HER2 status and Ki-67 labelling index (8).Despite improvements in the...

Fascin Induces Epithelial-Mesenchymal Transition of Cholangiocarcinoma Cells by Regulating Wnt/β-Catenin Signaling

“…Fascin is widely expressed in normal mesenchymal tissues and in the nervous system, but not in normal epithelial cells. Fascin is increased in several types of cancers, such as breast, colon, esophagus, and gastric cancers [ 16 – 19 ]. More recently, it was reported that Fascin overexpression leads to EMT, which plays a central role in carcinoma progression and metastasis [ 20 ].…”

Fascin overexpression is associated with higher grades of breast cancer

“…Similar to our findings, Monther Al-Alwan and et al have reported a strong relationship between the expression of fascin and basal-like breast cancer (p < 0.001), negative expression of ER (p < 0.001) and PR (p < 0.020), larger tumour size (p = 0.091) and distant metastasis (p = 0.017) [25]. Some other studies have also reported higher expression of Fascin in triple negative or high grade tumours [13,14,26].…”

“…Recent studies have reported overexpression of fascin in several types of malignancies, including lung [8], colon [9], stomach [10], ovary [11] and breast [12]. Previous studies on breast cancer have shown that fascin expression was associated with poor prognosis and some studies have suggested to use fascin as a potential therapeutic target especially in triple negative tumors [13,14,15]. In this study, we tried to evaluate the expression of fascin in human breast cancer using immunohistochemistry (IHC) method and explore its correlation with clinicopathological findings.…”

Fascin is involved in cancer cell invasion and is regulated by stromal factors

“…In previous array-CGH studies, fascin showed a higher expression level in cancer specimens than that in normal specimens and dysplasia (10). Fascin has been reported to be involved in cancer invasion and has been proposed as a diagnostic marker for several tumors including breast, prostate and esophageal squamous cell carcinoma (20)(21)(22)(23)(24)(25). Nevertheless, understanding of mechanisms underlying the significance of fascin expression in cancer cells is unknown, and further studies are needed.…”