FSCN1 and epithelial mesenchymal transformation transcription factor expression in human pancreatic intraepithelial neoplasia and ductal adenocarcinoma.

BACKGROUND:The actin regulatory protein fascin (FSCN1) and epithelial mesenchymal transition (EMT) transcription factor (TF) SLUG/SNAI2 have been shown to be expressed in PDAC and its precursor lesions (pancreatic intraepithelial neoplasia (PanIN), graded 1-3) in in vitro and murine in vivo studies. Our aim was to investigate the expression of FSCN1 and EMT-TFs and their association with survival in human PanIN and PDAC. METHODS:Expression was investigated in silico using TCGA PanCancer Atlas data (177 PDAC samples with mRNA data) and immunohistochemical staining of a tissue microarray (TMA) (59 PDAC patients). RESULTS:High FSCN1 expression was associated with poorer overall survival (p = 0.02) in the TCGA data. EMT-TF expression was not associated with survival, however FSCN1 expression correlated with that of the EMT-TFs SLUG/SNAI2 (rho = 0.49, p < 0.001) and TWIST1 (rho = 0.52, p < 0.001). TMA IHC showed low expression of SNAI2 and TWIST1 in normal ductal epithelium, while FSCN1 was not expressed. SNAI2 increased slightly in PanIN1-2, then decreased in higher grade lesions. TWIST1 increased in PanIN2-3 and was retained in PDAC. FSCN1 was increasingly expressed from PanIN2 onwards. SNAI2 and TWIST1 expression positively correlated in all grades of PanIN and PDAC (rho = 0.52, p < 0.001). FSCN1 correlated positively with SNAI2 in PanIN1 (rho = 0.56, p < 0.01). CONCLUSIONS:Increased expression of EMT-TFs in low-grade PanIN followed by FSCN1 in PanIN3 and PDAC suggests EMT-TFs may trigger FSCN1 expression and are potential early diagnostic markers. FSCN1 expression correlated with overall survival in PDAC and may have value as a prognostic marker.