Coexpression of Arp2 and WAVE2 predicts poor outcome in invasive breast carcinoma
Coexpression of Arp2 and WAVE2 predicts poor outcome in invasive breast carcinoma
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DOI：
10.1038/modpathol.3800741
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发表时间：
2007-03-01
期刊：
影响因子：
7.5
通讯作者：
Mukai, Kiyoshi
中科院分区：
文献类型：
--
作者：
Iwaya, Keiichi;Norio, Kohno;Mukai, Kiyoshi
组织学分级高的乳腺癌具有高度侵袭性和转移性。其不规则形态的一个原因是由于分支肌动蛋白丝网络的聚集而形成过度突起。在哺乳动物细胞中，肌动蛋白相关蛋白2和3（Arp 2/3）复合物通过与Wiskott-Aldrich综合征（WASP）/WASP家族的维脯氨酸同源蛋白2（WAVE 2）（WASP蛋白家族的一个成员）结合来启动肌动蛋白组装以形成片状脂质突起。在这项研究中，定位Arp 2和WAVE 2在乳腺癌进行了调查，以澄清是否与组织学分级或患者的结果与这两种蛋白的共表达。对197例乳腺癌的镜像标本进行Arp 2和WAVE 2的免疫组织化学染色，并研究这两种蛋白的共表达与临床病理因素之间的关系。Kaplan-Meier无病生存和总生存曲线分析Arp 2和WAVE 2共表达在乳腺癌中的预后意义。在179例浸润性导管癌中有64例（36%）和18例导管原位癌中有2例（11%）同时检测到Arp 2和WAVE 2的表达，但在任何邻近的非癌组织中均未检测到。同时表达Arp 2和WAVE 2的癌细胞比例在组织学分级高（P < 0.0001）和有淋巴结转移者（P=0.0150）中明显增高。与癌细胞仅表达Arp 2和WAVE 2之一或不表达的患者相比，癌细胞显示这种共表达的患者的无病生存期（P =0.0002）和总生存期（P=0.0122）较短。多因素考克斯回归分析显示Arp 2和WAVE 2的共表达是肿瘤复发（P=0.0308）和死亡（P=0.0455）的独立因素。这些结果表明，Arp 2和WAVE 2的共表达是一个重要的预后因素，与乳腺浸润性导管癌的侵袭性形态密切相关。
Breast carcinoma with a high histologic grade is highly invasive and metastatic. One reason for its irregular morphology is the formation of excessive protrusions due to assemblages of branched actin filament networks. In mammalian cells, the actin-related protein 2 and 3 (Arp2/3) complex initiates actin assembly to form lamellipodial protrusions by binding to the Wiskott-Aldrich syndrome (WASP)/WASP family verproline-homologous protein2 (WAVE2), a member of the WASP protein family. In this study, the localization Arp2 and WAVE2 in breast carcinoma was investigated to clarify whether coexpression of the two proteins is associated with histologic grade or patient outcome. Immunohistochemical staining of Arp2 and WAVE2 was performed on mirror specimens of 197 breast carcinomas, and the association between coexpression of the two proteins and clinicopathologic factors was examined. Kaplan-Meier disease-free survival and overall survival curves were analyzed to determine the prognostic significance of Arp2 and WAVE2 coexpression in breast carcinoma. Coexpression of Arp2 and WAVE2 was detected in 64 (36%) of 179 invasive ductal carcinomas and in 2 (11%) of 18 ductal carcinomas in situ, but was not detected in any adjacent non-cancerous tissue. The proportion of cancer cells expressing both Arp2 and WAVE2 was significantly higher in cases with high histologic grade (P < 0.0001), and cases with lymph node metastasis (P=0.0150). The patients whose cancer cells showed such coexpression had shorter disease-free (P=0.0002) and overall survival (P=0.0122) than patients whose cancer cells expressed only one or none of Arp2 and WAVE2. Multivariate Cox regression analysis revealed that coexpression of Arp2 and WAVE2 is an independent factor for both tumor recurrence (P=0.0308) and death (P=0.0455). These results indicate that coexpression of Arp2 and WAVE2 is a significant prognostic factor that is closely associated with aggressive morphology of invasive ductal carcinoma of the breast.