Actinin-4 expression in ovarian cancer: a novel prognostic indicator independent of clinical stage and histological type
Actinin-4 expression in ovarian cancer: a novel prognostic indicator independent of clinical stage and histological type
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DOI：
10.1038/modpathol.3800966
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发表时间：
2007-12-01
期刊：
影响因子：
7.5
通讯作者：
Matsubara, Osamu
中科院分区：
文献类型：
--
作者：
Yamamoto, Sohei;Tsuda, Hitoshi;Matsubara, Osamu
肌动蛋白-4是非肌肉α-肌动蛋白和肌动蛋白捆绑蛋白的同种型。通过增强细胞运动性，辅肌动蛋白-4显示出与非肌辅肌动蛋白的另一种亚型“辅肌动蛋白-1”不同的生物学特性，并且辅肌动蛋白-4在一些人类恶性肿瘤如乳腺癌、肺癌和结肠直肠癌中的可变临床病理学意义已经被证明。我们在此描述了肌动蛋白-4在卵巢癌中表达的临床病理学和预后意义。我们对265例原发性卵巢癌（浆液性116例，透明细胞71例，类浆液性43例，粘液腺癌35例）中的肌动蛋白-4表达进行了免疫组化分析。参照内皮细胞免疫反应性，肌动蛋白-4的胞浆表达分为低（包括阴性）或高。然后，各种参数，如患者的特征，组织病理学结果，包括E-钙粘蛋白和β-连环蛋白免疫反应，和临床结果，进行了比较，组之间的差异，在强度或细胞内分布的肌动蛋白-4免疫反应。在137例（57%）病例中证实了actinin-4的高表达，并与浆液性组织学有关（P=0.0075），高组织学分级（P < 0.0001），疾病晚期（P=0.036），初次手术后高度残留疾病（P=0.0047），患者结局较差（5年生存率：高表达组为52.4%，低表达组为71.9%，对数秩检验P=0.0043），E-cadherin表达减少，β-catenin表达保留（P分别为0.0097和0.017）。20例（7.5%）检测到肌动蛋白-4的核免疫反应性，与低组织学分级相关（P=0.0079），但与其他变量无关。多变量分析显示，高辅肌动蛋白-4表达是一个独立的预后因素，总生存率，以及高程度的残留疾病和透明细胞组织学。辅肌动蛋白-4在细胞质中的积累可能与肿瘤侵袭和转移的更高倾向有关，可能通过增强细胞运动性，并且可能是卵巢癌患者的新的预后指标。
Actinin-4 is an isoform of non-muscular alpha-actinin and actin-bundling protein. By enhancing cell motility, actinin-4 shows different biological properties from another isoform of non-muscular actinin 'actinin-1' and variable clinicopathological implications of actinin-4 have been demonstrated in some human malignancies such as breast cancers, lung cancers, and colorectal cancers. We herein described the clinicopathological and prognostic significance of actinin-4 expression in ovarian cancers. Actinin-4 expression was analyzed immunohistochemically in 265 primary ovarian carcinomas: 116 serous, 71 clear cell, 43 endometrioid, and 35 mucinous adenocarcinomas. With reference to endothelial immunoreactivity, cytoplasmic expression of actinin-4 was classified as either low ( including negative) or high. Then, various parameters such as patients' characteristics, histopathological findings including E-cadherin and beta-catenin immunoreactivity, and clinical outcome, were compared between groups showing differences in the intensity or intracellular distribution of actinin-4 immunoreactivity. High expression of actinin-4 was demonstrated in 137 (57%) cases and was associated with serous histology ( P=0.0075), high histological grade ( P < 0.0001), an advanced disease stage (P=0.036), a high degree of residual disease after initial surgery (P=0.0047), poor patient outcome (5-year survival: 52.4% in the high-expression group vs 71.9% in the low expression group, P=0.0043 by log-rank test), and also with reduced E-cadherin and preserved beta-catenin expressions (P=0.0097 and 0.017, respectively). Nuclear immunoreactivity for actinin-4 was detected in 20 (7.5%) cases and was associated with low histological grade (P=0.0079) but not with other variables. Multivariate analysis showed that high actinin-4 expression was an independent prognostic factor for overall survival, as well as a high degree of residual disease and clear-cell histology. Accumulation of actinin-4 in the cytoplasm may be related to a higher propensity for tumor invasiveness and metastasis, probably by enhancing cell motility, and could be a novel prognostic indicator for patients with ovarian carcinomas.