Zhang Jian, Yang Fei, Ding Yong, Zhen Linlin, Han Xuedong, Jiao Feng, Tang Jinhai
Department of General Surgery, Nanjing Medical University Affiliated Jiangsu Cancer Hospital Nanjing 210009, China ; Department of General Surgery, Huai'an First People's Hospital, Nanjing Medical University Huai'an, Jiangsu 223300, China.
Department of Oncology, Huai'an Second People's Hospital Huai'an, Jiangsu 223002, China.
Int J Clin Exp Pathol. 2015 Aug 1;8(8):9240-7. eCollection 2015.
L1 cell adhesion molecule (L1CAM) has been observed to be aberrantly expressed and implicated in progression of several types of human cancers. However, its roles in breast cancer have not been fully elucidated. In this study, we aimed to investigate the clinical significance of L1CAM in human breast cancer and to validate whether it participates in cancer cell migration and invasion.
Immunohistochemical analysis of 100 breast cancer and matched non-cancerous breast tissues was performed to detect the expression and sub-cellular localization of L1CAM protein. Its associations with clinicopathological characteristics of breast cancer patients were statistically analyzed and its phenotypic effects were also evaluated in vitro.
Of the 100 breast cancer patients, 89 (89.0%) were positive for L1CAM immunostaining localized in the membrane of cancer cells. The immunoreactive scores of L1CAM protein in breast cancer tissues were significantly higher than those in matched non-cancerous breast tissues (P<0.05). Chi-Square analysis showed the significant associations between L1CAM overexpression and high tumor stage (P=0.01), advanced tumor grade (P=0.03), positive lymph node metastasis (P=0.01) and tumor recurrence (P=0.01) in breast cancer patients. Moreover, we found that RNA interference-mediated knockdown of L1CAM could inhibit the migration and invasion abilities of breast cancer cells in vitro.
Our results suggest that the overexpression of L1CAM may be related to several established markers of poor prognosis in breast cancer patients. L1CAM might be a potential therapeutic target against metastatic breast cancer.
已观察到L1细胞粘附分子(L1CAM)在几种人类癌症进展中异常表达并发挥作用。然而,其在乳腺癌中的作用尚未完全阐明。在本研究中,我们旨在探讨L1CAM在人类乳腺癌中的临床意义,并验证其是否参与癌细胞的迁移和侵袭。
对100例乳腺癌及配对的癌旁乳腺组织进行免疫组织化学分析,以检测L1CAM蛋白的表达及亚细胞定位。对其与乳腺癌患者临床病理特征的相关性进行统计学分析,并在体外评估其表型效应。
100例乳腺癌患者中,89例(89.0%)L1CAM免疫染色阳性,定位于癌细胞膜。乳腺癌组织中L1CAM蛋白的免疫反应评分显著高于配对的癌旁乳腺组织(P<0.05)。卡方分析显示,L1CAM过表达与乳腺癌患者的高肿瘤分期(P=0.01)、高肿瘤分级(P=0.03)、阳性淋巴结转移(P=0.01)及肿瘤复发(P=0.01)显著相关。此外,我们发现RNA干扰介导的L1CAM敲低可抑制体外乳腺癌细胞的迁移和侵袭能力。
我们的结果表明,L1CAM的过表达可能与乳腺癌患者几种已确立的不良预后标志物有关。L1CAM可能是转移性乳腺癌的一个潜在治疗靶点。