Enhanced karyopherin-α2 expression is associated with carcinogenesis in patients with intraductal papillary mucinous neoplasms

Enhanced karyopherin-α2 expression is associated with carcinogenesis in patients with intraductal papillary mucinous neoplasms
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DOI:
10.1016/j.pan.2017.04.011
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发表时间:
2017-07-01
期刊:
影响因子:
3.6
通讯作者:
Shirabe, Ken
Shirabe, Ken
中科院分区:
医学3区
文献类型:
--
作者:
Kubo, Norio;Araki, Kenichiro;Shirabe, Ken

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背景/目的:导管内乳头状黏液性肿瘤(IPMN)可恶变。核仁组成蛋白-α2(KPNA2)在核质转运中起核心作用,与多种癌症有关。方法:采用免疫组织化学方法检测40例手术切除的IPMN组织中KPNA2的表达,分析其与临床病理因素及Ki-67表达的关系。结果:18例IPMN组织中KPNA2表达阳性,占45%。浸润性癌IPMN组织中KPNA2的表达水平显著高于癌旁正常组织和低、高级别不典型增生组织。KPNA2表达与病理恶性程度和Ki-67标记指数相关,KPNA2和Ki-67共同定位于细胞核。在KPNA2高表达的IPMN组织中,E2F与KPNA2共定位。KPNA2在侵袭前沿和增殖中的Ki-67阳性细胞中表达增强。此外,KPNA2在IPMN组织中的表达与年龄、主胰管直径扩张、结节的存在和组织学类型有关。(C)2017年国际行动计划和环境影响评估。爱思唯尔出版,版权所有。
Background/objectives: Intraductal papillary mucinous neoplasms (IPMN) can become malignant. Karyopherin-alpha 2 (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.Methods: KPNA2 expression was investigated by immunohistochemistry in 40 surgically resected IPMN samples and its association with clinicopathological factors and Ki-67 expression were examined.Results: 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.Conclusion: KPNA2 expression is associated with carcinogenesis of IPMN through the adenoma-carcinoma sequence. (C) 2017 IAP and EPC. Published by Elsevier B.V. All rights reserved.