Fascin is associated with aggressive behavior and poor outcome in uterine carcinosarcoma

Abstract

Objective The mechanisms underlying the histogenesis and aggressiveness of uterine carcinosarcoma (UCS) are poorly understood; however, previous studies implicate epithelial-mesenchymal transition (EMT). Fascin is a proinvasive, actin-bundling protein and an important component of EMT. It is associated with poor outcomes in human carcinoma, especially in estrogen receptor (ER)-negative tumors arising in organs normally expressing ER. We sought to evaluate fascin expression in UCS and its relationship to ER status, clinicopathologic indicators of tumor aggressiveness, and survival outcomes. Method Forty-four surgically staged cases of UCS were immunohistochemically evaluated for fascin and estrogen receptor-expression and correlated with clinicopathologic parameters derived from electronic medical records and pathology reports. Results Fascin was only expressed in malignant epithelium and mesenchyma and was uniformly absent in background benign counterparts. Increased expression was associated with extrapelvic disease (P = 0.028), higher stage (P = 0.021), larger tumor size (P = 0.032), shorter progression-free interval (P = 0.035), and reduced estrogen receptor-expression (P = 0.04). Conclusion Fascin is aberrantly expressed in both elements of UCS and is associated with aggressive behavior and worse outcome. As a component of EMT and mediator of invasion, fascin may serve as a target in future therapies.