Original Article

Modern Pathology (2007) 20, 552–561. doi:10.1038/modpathol.3800763; published online 30 March 2007

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

Hiroshi Yamaguchi1, Takahiro Inoue1, Takashi Eguchi1,4, Yoshihiro Miyasaka1, Kenoki Ohuchida2, Kazuhiro Mizumoto2, Tomomi Yamada3, Koji Yamaguchi2, Masao Tanaka2 and Masazumi Tsuneyoshi1

  1. 1Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
  2. 2Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
  3. 3Department of Medical Information Science, Kyushu University Hospital, Fukuoka, Japan
  4. 4Department of Pathology, Iizuka Hospital, Iizuka, Japan

Correspondence: Dr H Yamaguchi, MD, Department of Anatomic Pathology, Pathological Sciences, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan. E-mail: h-yama@surgpath.med.kyushu-u.ac.jp

Received 20 October 2006; Revised 17 January 2007; Accepted 18 January 2007; Published online 30 March 2007.

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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 pre-cancerous 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%) (P<0.05, 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%) (P<0.05). 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. Fascin could become a new therapeutic target for inhibition of their progression.

Keywords:

intraductal papillary mucinous neoplasm, fascin, immunohistochemistry, laser microdissection, real-time RT-PCR, phenotypic subclassification

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