Actinin-4 Expression in Primary and Metastasized Pancreatic Ductal Adenocarcinoma
Actinin-4 Expression in Primary and Metastasized Pancreatic Ductal Adenocarcinoma
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DOI：
10.1097/mpa.0b013e3181b28d6f
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发表时间：
2009-11-01
期刊：
影响因子：
2.9
通讯作者：
Schmidt, Jan
中科院分区：
文献类型：
--
作者：
Welsch, Thilo;Keleg, Shereen;Schmidt, Jan
目的：Actinin-4是一种肌动蛋白捆绑蛋白，可能在多种实体瘤中具有促肿瘤作用。本研究分析了actinin-4在胰腺、局限性和转移性胰腺导管腺癌（PDAC）中的表达及其与临床预后的关系。对38例胰腺导管腺癌组织、15例淋巴结转移瘤、10例肝转移瘤、正常胰腺和4株PDAC细胞系进行免疫组化检测，结果：在正常胰腺组织中，actinin-4主要表达于导管细胞。在PDAC，肿瘤细胞表现出强烈的，但差异细胞质免疫反应辅肌动蛋白-4。多变量分析显示，肌动蛋白-4免疫反应性，高龄，未分化的等级作为重要的预后因素与PDAC切除术后生存率较差。与原发肿瘤相比，转移到淋巴结或肝脏的细胞表现出肌动蛋白-4没有显着增加。在任何PDAC样品和4种细胞系中均未观察到核染色。在PDAC细胞中，肌动蛋白-4定位于动态肌动蛋白结构和invadopodia.Conclusions：肌动蛋白-4表达水平显着相关PDAC切除术后生存较差。尽管有报道称辅肌动蛋白-4会促进淋巴结转移，但在PDAC转移灶中并没有增强表达。
Objectives: Actinin-4 is an actin-bundling protein that probably has a tumor-promoting potential in several solid tumors. The present study analyzed the expression of actinin-4 in the pancreas, in localized and metastasized pancreatic ductal adenocarcinoma (PDAC), and the correlation with clinical outcome.Methods: Pancreatic ductal adenocarcinoma tissue from 38 patients, 15 lymph node and 10 liver metastases, normal pancreas, and 4 PDAC cell lines, were examined by immunohistochemistry, and actinin-4 expression was quantified by immunofluorescence analysis.Results: In the normal pancreas, actinin-4 was most prominently expressed in ductal cells. In PDAC, tumor cells exhibited strong but differential cytoplasmic immunoreactivity for actinin-4. A multivariate analysis revealed actinin-4 immunoreactivity, advanced age, and undifferentiated grade as significant prognostic factors associated with worse survival after PDAC resection. Cells metastasized to lymph nodes or to the liver exhibited no significant increase of actinin-4 compared with the primary tumors. A nuclear staining was observed neither in any of the PDAC samples nor in the 4 cell lines. In PDAC cells, actinin-4 localized to dynamic actin structures and to invadopodia.Conclusions: Actinin-4 expression levels significantly correlate with worse survival after PDAC resection. Although actinin-4 has been reported to promote lymph node metastases, there was no enhanced expression in PDAC metastases.