Kubo Norio, Araki Kenichiro, Altan Bolag, Hoshino Kouki, Ishii Norihiro, Tsukagoshi Mariko, Igarashi Takamichi, Watanabe Akira, Kato Toshihide, Hirai Keitaro, Yokobori Takehiko, Saito Fumiyoshi, Suzuki Hideki, Kuwano Hiroyuki, Shirabe Ken
Department of Hepatobiliary and Pancreatic Surgery, Gunma University, Graduate School of Medicine, Japan; Department of General Surgical Science, Gunma University, Graduate School of Medicine, Japan.
Department of Hepatobiliary and Pancreatic Surgery, Gunma University, Graduate School of Medicine, Japan; Department of General Surgical Science, Gunma University, Graduate School of Medicine, Japan.
Pancreatology. 2017 Jul-Aug;17(4):611-616. doi: 10.1016/j.pan.2017.04.011. Epub 2017 Apr 23.
BACKGROUND/OBJECTIVES: Intraductal papillary mucinous neoplasms (IPMN) can become malignant. Karyopherin-α2 (KPNA2) plays a central role in nucleocytoplasmic transport and is associated with various types of cancer. The current study examined pancreatic KPNA2 expression in cancer patients and evaluated its association with clinicopathological factors, cancer cell proliferation.
KPNA2 expression was investigated by immunohistochemistry in 40 surgically resected IPMN samples and its association with clinicopathological factors and Ki-67 expression were examined.
Eighteen IPMN samples (45% of patients) showed positive KPNA2 expression. KPNA2 expression levels in IPMN tissue with invasive carcinoma were significantly higher than those in adjacent normal tissues and in IPMN tissue with low-to high-grade dysplasia. KPNA2 expression correlated with pathological malignancy and Ki-67 labeling index and KPNA2 and Ki-67 expression was co-localized in nuclei. E2F were co-localized with KPNA2 in the IPMN tissues with high expression of KPNA2. KPNA2 expression was enhanced in the invasion front and in proliferating Ki-67-positive cells. In addition, KPNA2 expression in IPMN tissues was associated with older age, dilation of main pancreatic duct diameter, the presence of nodules, and histological type.
KPNA2 expression is associated with carcinogenesis of IPMN through the adenoma-carcinoma sequence.
背景/目的：导管内乳头状黏液性肿瘤（IPMN）可发生恶变。核转运蛋白α2（KPNA2）在核质转运中起核心作用，且与多种类型癌症相关。本研究检测了癌症患者胰腺中KPNA2的表达，并评估其与临床病理因素、癌细胞增殖的关系。
采用免疫组织化学法检测40例手术切除的IPMN样本中KPNA2的表达，并检测其与临床病理因素及Ki-67表达的关系。
18例IPMN样本（占患者的45%）显示KPNA2表达阳性。浸润性癌的IPMN组织中KPNA2表达水平显著高于相邻正常组织及低级别至高级别异型增生的IPMN组织。KPNA2表达与病理恶性程度及Ki-67标记指数相关，且KPNA2和Ki-67表达在细胞核中共定位。在KPNA2高表达的IPMN组织中，E2F与KPNA2共定位。KPNA2表达在侵袭前沿及增殖的Ki-67阳性细胞中增强。此外，IPMN组织中KPNA2表达与年龄较大、主胰管直径扩张、结节的存在及组织学类型有关。
KPNA2表达通过腺瘤-癌序列与IPMN的致癌作用相关。
