Analysis of novel tumor markers in pancreatic and biliary carcinomas using tissue microarrays

Swierczynski, Sharon L.; Maitra, Anirban; Abraham, Susan C.; Iacobuzio‐Donahue, Christine A.; Ashfaq, Raheela; Cameron, John L.; Schulick, Richard D.; Yeo, Charles J.; Rahman, Asifur; Hinkle, David A.; Hruban, Ralph H.; Argani, Pedram

doi:10.1016/j.humpath.2003.10.012

Cited by 133 publications

(91 citation statements)

References 35 publications

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“…18,19,21,23,24,26,33 Among the pancreatic neoplasms, IacobuzioDonahue et al 42 reported fascin upregulation for the first time in ductal adenocarcinoma using cDNA microarrays (13-fold overexpression of fascin transcripts in ductal adenocarcinoma compared with normal tissues). Immunohistochemical studies then confirmed fascin overexpression, not only in infiltrating ductal adenocarcinomas 28,30,31 but also in PanINs. 29,30 The fact that PanINs show fascin upregulation correlated with histological grade increased our interest in fascin expression in IPMNs, because PanINs and IPMNs share the following fundamental characteristics: 5,6 inherently intraductal; composed predominantly of columnar, mucin-producing cells that may grow in a flat configuration or may produce papillae; exhibit a range of cytologic and architectural atypia (mild, moderate and severe); recognized as precursors to Fascin expression in IPMNs of the pancreas H Yamaguchi et al invasive adenocarcinoma; and sequentially accumulate similar genetic alterations with increasing cytoarchitectural atypia.…”

Section: Discussionmentioning

confidence: 78%

“…It is required for the formation of actin-based cell-surface protrusions that are essential for cellular migration and cellmatrix adhesion. [15][16][17] In normal epithelial cells, fascin expression is usually absent or very low, but it is significantly upregulated in transformed epithelial cells and several types of human carcinoma such as lung, 18,19 breast, [20][21][22][23] esophagus, 24,25 stomach, 26 colon, 27 pancreas, [28][29][30][31] biliary tract and ampulla, 31,32 ovary, 33 urinary bladder, 34 and skin. 35 Among the above neoplasms, fascin upregulation is most frequently observed in pancreatic infiltrating adenocarcinoma.…”

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confidence: 99%

“…35 Among the above neoplasms, fascin upregulation is most frequently observed in pancreatic infiltrating adenocarcinoma. 28,30,31 It is interesting that PanIN shows fascin expression despite being an intraepithelial neoplasia. 29,30 In general, in tumors of other organs, expression of fascin is especially strong in areas of infiltration, or is limited to such areas.…”

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

et al. 2007

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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.

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Section: Discussionmentioning

confidence: 78%

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confidence: 99%

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confidence: 99%

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

et al. 2007

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“…20,24 However, in contrast to most malignancies, gene expression profiling as well as tissue microarray screens have recently demonstrated overexpression of 14-3-3s in pancreatic ductal adenocarcinomas and biliary cancers. 28,29 Interestingly, deregulated overexpression of 14-3-3s was associated with CpG island hypomethylation. Close association of CpG island hypomethylation with overexpression of multiple genes indicates that gene hypomethylation is a frequent epigenetic event in pancreatic cancer.…”

Section: Discussionmentioning

confidence: 99%

Downregulation of 14-3-3σ in ovary, prostate and endometrial carcinomas is associated with CpG island methylation

et al. 2005

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“…[11][12][13][17][18][19][20] Interestingly, fascin overexpression was closely correlated with the invasiveness of esophageal carcinoma cells, and overproduction of matrix metalloproteinase2 (MMP2) and MMP9 was involved in fascin-mediated carcinoma invasion. 21 Recently, it was also reported that fascin was overexpressed in cholangiocarcinoma (CC); [22][23][24][25] however, the clinicopathological significance of fascin expression in CC is still unclear. In particular, it has not been elucidated how fascin is involved in the development and progression of CC.…”

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Fascin is involved in tumor necrosis factor-α-dependent production of MMP9 in cholangiocarcinoma

Onodera

Zen

Harada

et al. 2009

Laboratory Investigation

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Fascin is an actin-binding protein involved in the cell motility. Recently, aberrant expression of fascin in carcinoma cells was reported to participate in their invasive growth in cooperation with proteinases such as matrix metalloproteinases (MMPs). This study examined the participation of fascin in the progression of cholangiocarcinoma (CC) with reference to MMPs and tumor necrosis factor-a (TNF-a). Expression levels of fascin and MMP2 and 9 were examined immunohistochemically in human non-neoplastic biliary epithelium (13 cases) and CC (87 cases). The relationship between fascin and MMP9-expression levels was examined using two CC cell lines (CCKS-1 and HuCCT1). It was also examined whether or not fascin was involved in TNF-a-induced overproduction of MMP9 in CC. Fascin and MMP9 were expressed in 49 and 53% of CC samples, respectively, and the expression of these genes was frequent in intrahepatic CC. Fascin expression was correlated significantly with MMP9 expression. In particular, these two molecules were expressed more intensely at the invasive fronts of CC. Fascin expression was an unfavorable prognostic factor for patients with intrahepatic CC. In vitro studies showed that TNF-a could induce the overexpression of fascin and MMP9 in two CC cell lines. A knockdown study of fascin by siRNA showed that TNF-a induced the overproduction of fascin, which in turn upregulated MMP9 expression. Overexpression of fascin may have an important function in the progression of CC, and fascin expression might be involved in the signaling pathway in TNF-a-dependent production of MMP9 in CC.

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Analysis of novel tumor markers in pancreatic and biliary carcinomas using tissue microarrays

Cited by 133 publications

References 35 publications

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

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

Downregulation of 14-3-3σ in ovary, prostate and endometrial carcinomas is associated with CpG island methylation

Fascin is involved in tumor necrosis factor-α-dependent production of MMP9 in cholangiocarcinoma

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