Bartova M, Hlavaty J, Tan Y, Singer C, Pohlodek K, Luha J, Walter I
2nd Department of Obstetrics and Gynecology, University Hospital Bratislava, Ružinovská 6, Bratislava, 826 06, Slovakia.
Department of Pathobiology, Institute of Anatomy, Histology and Embryology, University of Veterinary Medicine, Veterinärplatz 1, 1210, Vienna, Austria.
Clin Exp Metastasis. 2017 Jun;34(5):333-344. doi: 10.1007/s10585-017-9853-y. Epub 2017 Jun 17.
Ezrin, radixin, moesin (ERM) are important membrane-cytoskeletal crosslinkers and are suggested to play important role in cancer progression and metastasis. Even though ERM proteins were generally considered to be functionally redundant and the most studied was ezrin, recent studies highlight their distinct roles in metastatic process. Little information is available regarding the role of individual ERM proteins and their phosphorylated forms in human breast cancer. Our study is the first to examine expression of ezrin, moesin and their phosphorylated forms in primary breast tumors and matched lymph node metastases (LNMs) and their correlation with clinicopathological variables. A total of 88 primary breast cancer, 91 LNMs, 54 intraductal carcinoma and 26 normal adjacent breast tissue samples from tissue microarrays were studied. Expression was determined by immunohistochemistry, the intensity and number of positive cells was scored. Statistical analysis of protein expression and patients' age, tumor grade and hormonal status was performed. No statistical significant difference was found in ezrin, moesin, p-ezrinTyr353 and pan-p-ezrinThr567/radixinThr564/moesinThr558 expression between primary tumors and LNMs. Even though it was not significant, moesin expression varied between primary tumors, intraductal carcinoma, normal breast adjacent tissue and LNMs. A significant positive correlation between moesin and tumor grade has been proven. Even though primary tumors and matched LNMs did not show different expression patterns, moesin correlated significantly with higher tumor grade. Its positivity in intraductal carcinoma and normal breast tissue adjacent to cancer might indicate its role in tumor intiation/progression.
埃兹蛋白、根蛋白、膜突蛋白(ERM)是重要的膜细胞骨架交联蛋白,被认为在癌症进展和转移中发挥重要作用。尽管ERM蛋白通常被认为功能冗余,且研究最多的是埃兹蛋白,但最近的研究突出了它们在转移过程中的不同作用。关于个体ERM蛋白及其磷酸化形式在人类乳腺癌中的作用,目前所知甚少。我们的研究首次检测了原发性乳腺肿瘤及配对的淋巴结转移灶(LNMs)中埃兹蛋白、膜突蛋白及其磷酸化形式的表达情况,以及它们与临床病理变量的相关性。我们研究了来自组织芯片的88例原发性乳腺癌、91例LNMs、54例导管内癌和26例正常乳腺相邻组织样本。通过免疫组织化学测定表达情况,对阳性细胞的强度和数量进行评分。对蛋白表达与患者年龄、肿瘤分级和激素状态进行了统计分析。原发性肿瘤和LNMs之间在埃兹蛋白、膜突蛋白、磷酸化埃兹蛋白Tyr353以及泛磷酸化埃兹蛋白Thr567/根蛋白Thr564/膜突蛋白Thr558的表达上未发现统计学显著差异。尽管差异不显著,但膜突蛋白在原发性肿瘤、导管内癌、正常乳腺相邻组织和LNMs之间的表达有所不同。已证实膜突蛋白与肿瘤分级之间存在显著正相关。尽管原发性肿瘤和配对的LNMs未表现出不同的表达模式,但膜突蛋白与较高的肿瘤分级显著相关。其在导管内癌和癌旁正常乳腺组织中的阳性表达可能表明其在肿瘤起始/进展中的作用。