Fascin overexpression in intraductal papillary mucinous neoplasms (adenomas, borderline neoplasms, and carcinomas) of the pancreas, correlated with increased histological grade

Abstract

Intraductal papillary mucinous neoplasm (IPMN) is a well-established entity in pancreatic neoplasms and a precursor of infiltrating adenocarcinoma. Fascin, an actin-bundling protein involved in cellular motility, is upregulated in many human neoplasms. Its overexpression in pancreatic intraepithelial neoplasia, a precancerous lesion sharing many characteristics with IPMN, has been reported. However, fascin expression in IPMN remains unknown. The aim of this study was to investigate fascin expression in IPMNs and to elucidate its relationship to clinicopathological features, including histological grade and phenotypic subclassification. We evaluated fascin expression by immunohistochemistry in 116 surgical specimens, followed by quantitative analysis of fascin mRNA expression using a laser microdissection system and real-time reverse-transcriptase polymerase chain reaction in eight frozen samples. Fascin expression was significantly higher in borderline neoplasms (25/29, 86%) and carcinomas (37/42, 88%) than in adenomas (23/45, 51%) (Po0.05, respectively), but no difference was observed between borderline neoplasms and carcinomas. With regard to the subclassification, intestinal-type neoplasms (35/39, 90%) were more frequently positive for fascin than gastric-type neoplasms (36/59, 61%) (Po0.05). Two oncocytic-type neoplasms were both fascin-negative. Fascin mRNA expression seemed to be higher in moderately to severely dysplastic epithelium than in mildly dysplastic epithelium (not statistically significant), supporting the immunohistochemical experiments. Our findings suggest that fascin overexpression is involved in the progression of IPMN. Keywords: intraductal papillary mucinous neoplasm; fascin; immunohistochemistry; laser microdissection; realtime RT-PCR; phenotypic subclassification Intraductal papillary mucinous neoplasm (IPMN) is a well-established entity in pancreatic neoplasms. It was first reported in 1982 as a special type of pancreatic neoplasm with a characteristic endoscopic finding of extrusion of mucin through the ampulla of Vater. 1 At present, the term is used to unify tumors characterized by intraductal proliferation of neoplastic mucinous epithelium, which usually forms papillae and leads to cystic dilation of the pancreatic ducts. 2,3 Because IPMNs show a broad spectrum of dysplasia ranging from adenoma and borderline neoplasm to carcinoma in situ, the existence of an adenoma-carcinoma sequence is probable. In addition, some IPMNs are associated with infiltrating adenocarcinoma. Therefore, IPMN is gaining attention as a precursor of infiltrating adenocarcinoma in the pancreas as well as pancreatic intraepithelial neoplasia (PanIN). [4][5][6] Investigation of factors correlated with the progression of noninvasive and/or invasive IPMNs is important.

Fascin-1 overexpression and miR-133b downregulation in the progression of gastrointestinal stromal tumor

“…23 Although fascin-1 expression is absent or very low in the normal epithelium, it is upregulated in several types of carcinomas, including those of the lung, esophagus, stomach, colon, pancreas and urinary bladder. [24][25][26][27][28][29] Furthermore, overexpression of fascin-1 is correlated with worse prognosis and metastasis in several types of carcinomas. [25][26][27] The role of fascin-1 in carcinomas also has been probed experimentally in cell lines and mouse models.…”

Aberrant expression of cortactin and fascin are effective markers for pathogenesis, invasion, metastasis and prognosis of gastric carcinomas

“…One in vitro study revealed that all 33 ESCC cell lines expressed fascin protein at a certain level, and down-regulation of fascin expression reduced the motile and invasive properties in a fascin-overexpressed cell line (3). Fascin overexpression was positively linked to invasion, metastasis or staging in oral squamous, esophageal, colorectal, pancreatic and renal cell carcinoma at the level of protein or mRNA (3,13,(24)(25)(26). Moreover, ki-67, present in the nuclei of cells in the G 1 , S and G 2 phases of the cell cycle as well as in mitosis (27), was found to be highly expressed in fascin-positive areas, compared with fascinnegative areas (28).…”

“…In vitro experimental evidence indicated that fascin overexpression correlated with increased proliferation, altered ß1 integrin distribution, enhanced invasive capacity and an altered differentiation status in colonic adenocarcinoma (12). Up-regulated fascin induces a high potential for invasion and metastasis in various malignancies, including carcinomas of the pancreas, lung, esophagus and breast (3,8,13,14).…”

Phosphorylation of Fascin Decreases the Risk of Poor Survival in Patients With Esophageal Squamous Cell Carcinoma

“…It was named fascin because of its ability to form tight and stable bundles with F-actin (Kureishy et al 2002). Fascin is absent or shows very low expression in normal epithelium but is upregulated in transformed cells and in many kinds of human neoplasms, such as esophageal (Hashimoto et al 2005;Xue et al 2006), gastric (Hashimoto et al 2004), colonic (Hashimoto et al 2006), pancreatic (Yamaguchi et al 2007), lung (Pelosi et al 2003), breast (Rodríguez-Pinilla et al 2006), ovarian (Daponte et al 2008), prostate (Darnel et al 2009), and thyroid (Chen et al 2008) tumors, and high expression of fascin is associated with poor survival of patients.…”