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膜联蛋白 A1 的核定位与胃癌患者的晚期疾病和腹膜扩散相关。

Nuclear localization of annexin A1 correlates with advanced disease and peritoneal dissemination in patients with gastric carcinoma.

机构信息

Sir Run Run Shaw Institute of Clinical Medicine, College of Medicine, Zhejiang University and Key Laboratory of Biotherapy of Zhejiang Province, Hangzhou, China.

出版信息

Anat Rec (Hoboken). 2010 Aug;293(8):1310-4. doi: 10.1002/ar.21176.

DOI:10.1002/ar.21176
PMID:20665809
Abstract

Annexin A1 (ANXA1) is a multifunctional molecule, which mediates various important physiologic processes depending on its subcelluar localization. The purpose of this study was to investigate the expression of ANXA1 level and its subcellular localization in paired clinical samples of gastric adenocarcinoma and adjacent normal counterpart. The study also assesses the clinical significance of ANXA1 subcelluar localization in gastric adenocarcinoma. A total of 104 paired resected gastric adenocarcinoma and corresponding normal specimens were collected in this study. Expression of ANXA1 was examined by immunohistochemical staining. Both cytoplasmic and nuclear ANXA1 expression levels and their correlation with clinicopathological parameters were assessed. ANXA1 protein expression was positive in 72 of 104 (69.2%) normal tissues and 47 of 104 (45.2%) gastric adenocarcinoma tissues. ANXA1 staining was predominantly localized in the cytoplasm in all 72 ANXA1-positive normal specimens, whereas 12 ANXA1-positive gastric adenocarcinoma specimens showed positive nuclear staining. The positive nuclear staining correlated well with serosal invasion, peritoneal dissemination and TNM stage. Cases with positive nuclear staining presented more peritoneal dissemination (41.7%, 5/12) than those with negative nuclear staining (8.7%, 8/92; P = 0.007). A logistic regression model revealed that positive ANXA1 nuclear staining had an independent association with peritoneal dissemination (P = 0.039; hazards ratio, 9.499; 95% confidence interval, 1.159-77.815). These results indicated that ANXA1 is expressed in both gastric adenocarcinoma and normal tissues. In gastric adenocarcinoma tissues ANXA1 is expressed both in cytoplasm and nucleus and its nuclear localization correlates with advanced disease stage and peritoneal dissemination.

摘要

膜联蛋白 A1(ANXA1)是一种多功能分子,根据其亚细胞定位,介导各种重要的生理过程。本研究旨在探讨胃腺癌配对临床样本中 ANXA1 水平及其亚细胞定位的表达,并评估 ANXA1 亚细胞定位在胃腺癌中的临床意义。本研究共收集了 104 对胃腺癌和相应的正常组织标本。采用免疫组织化学染色法检测 ANXA1 的表达。评估细胞质和核 ANXA1 表达水平及其与临床病理参数的相关性。104 例正常组织中有 72 例(69.2%)和 47 例(45.2%)胃腺癌组织中 ANXA1 蛋白表达阳性。72 例 ANXA1 阳性的正常标本中 ANXA1 染色均主要定位于细胞质,而 12 例 ANXA1 阳性的胃腺癌标本显示核阳性染色。核阳性染色与浆膜浸润、腹膜扩散和 TNM 分期密切相关。核染色阳性的病例腹膜扩散更多(41.7%,5/12),而核染色阴性的病例腹膜扩散较少(8.7%,8/92;P=0.007)。逻辑回归模型显示,ANXA1 核阳性染色与腹膜扩散有独立相关性(P=0.039;危险比,9.499;95%置信区间,1.159-77.815)。这些结果表明,ANXA1 在胃腺癌和正常组织中均有表达。在胃腺癌组织中,ANXA1 既表达于细胞质又表达于细胞核,其核定位与疾病进展期和腹膜扩散相关。

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