DNA damage response and its clinicopathological relationship in appendiceal tumors
DNA damage response and its clinicopathological relationship in appendiceal tumors
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DOI：
10.1007/s00384-014-1996-6
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发表时间：
2014-08
影响因子：
2.8
通讯作者：
N. Yajima;R. Wada;Yutaka Matsuzaki;S. Yagihashi
中科院分区：
文献类型：
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作者：
N. Yajima;R. Wada;Yutaka Matsuzaki;S. Yagihashi
背景阑尾肿瘤是一种罕见的肿瘤，其发病机制尚不清楚。DNA损伤反应（DDR）是从检测到DNA损伤到修复的一系列过程，其损伤与癌症的进展有关。方法应用免疫组化方法检测4例腺瘤（adenoma，AD）、5例非粘液腺癌（non-mucinous adenocarcinoma，AC）、5例正常肾组织中Chk 2、磷酸化Chk 2（phosphorylated Chk 2，pChk 2）和TP 53的表达，并分析其与临床病理的关系。29例低度恶性阑尾粘液性肿瘤（LAMN）和7例粘液腺癌（MAC）。结果Chk 2在所有肿瘤细胞核中均呈高表达，在所有肿瘤细胞核中均呈高表达。虽然pChk 2在AD、LAMN和MAC中较高，但在AC中降低。TP 53在LAMN中的核阳性反应较其他肿瘤低。LAMN的Ki-67标记指数略低于其他肿瘤。LAMN的复发和死亡率较AC和MAC低。结论AC和MAC的DDR功能受损。DDR在LAMN中得以保留，这可能是LAMN低增殖活性和良好临床过程的原因。
BackgroundAppendiceal tumors are rare, and their pathogenesis is not well known. DNA damage response (DDR) is a sequence from the detection of damaged DNA to the repair, and its impairment is implicated in the progression of cancers. The aim of the current study is to explore the expression and phosphorylation of checkpoint kinase 2 (Chk2) and TP53, which are key molecules in DDR, and their clinicopathological correlation in the appendiceal tumors.MethodsChk2, phosphorylated Chk2 (pChk2), and TP53 were immunostained in 4 cases of adenoma (AD), 5 non-mucinous adenocarcinomas (AC), 29 low-grade appendiceal mucinous neoplasms (LAMN), and 7 mucinous adenocarcinomas (MAC). Ki-67 labeling index was also evaluated by immunostaining.ResultsChk2 was highly expressed in the nuclei of all the appendiceal tumors. While pChk2 was high in AD, LAMN, and MAC, it was reduced in AC. Nuclear positive reaction of TP53 was lower in LAMN compared with those of other tumors. The Ki-67 labeling index was slightly lower in LAMN than those in other tumors. The recurrence and death in LAMN is infrequent compared with those in AC and MAC.ConclusionsThe current study suggested the impairment of DDR in AC and MAC. DDR appeared to be preserved in LAMN, and it may account for low proliferating activity and a favorable clinical course in LAMN.