Yamaguchi Hiroshi, Inoue Takahiro, Eguchi Takashi, Miyasaka Yoshihiro, Ohuchida Kenoki, Mizumoto Kazuhiro, Yamada Tomomi, Yamaguchi Koji, Tanaka Masao, Tsuneyoshi Masazumi
Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Mod Pathol. 2007 May;20(5):552-61. doi: 10.1038/modpathol.3800763. Epub 2007 Mar 30.
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.
导管内乳头状黏液性肿瘤（IPMN）是胰腺肿瘤中一种已明确的实体，是浸润性腺癌的前体。Fascin是一种参与细胞运动的肌动蛋白捆绑蛋白，在许多人类肿瘤中上调。据报道，它在胰腺上皮内瘤变（一种与IPMN有许多共同特征的癌前病变）中过度表达。然而，Fascin在IPMN中的表达情况尚不清楚。本研究的目的是调查Fascin在IPMN中的表达，并阐明其与临床病理特征（包括组织学分级和表型亚分类）的关系。我们通过免疫组织化学评估了116例手术标本中Fascin的表达，随后使用激光显微切割系统和实时逆转录聚合酶链反应对8例冷冻样本进行了Fascin mRNA表达的定量分析。Fascin在交界性肿瘤（25/29，86%）和癌（37/42，88%）中的表达明显高于腺瘤（23/45，51%）（P均<0.05），但交界性肿瘤和癌之间未观察到差异。在亚分类方面，肠型肿瘤（35/39，90%）Fascin阳性的频率高于胃型肿瘤（36/59，61%）（P<0.05）。两个嗜酸性细胞型肿瘤均为Fascin阴性。Fascin mRNA表达在中度至重度发育异常上皮中似乎高于轻度发育异常上皮（无统计学意义），支持免疫组织化学实验。我们的研究结果表明，Fascin过度表达参与了IPMN的进展。Fascin可能成为抑制其进展的新治疗靶点。
