Department of Gynaecology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
J Clin Pathol. 2011 Feb;64(2):146-52. doi: 10.1136/jcp.2010.082602.
For prediction and understanding of underlying mechanisms of organ-specific metastases, various gene and protein expression signatures have been identified in primary breast carcinomas. These expression signatures often include several genes coding for adhesion molecules, such as activated leucocyte cell adhesion molecule (ALCAM/CD166) and carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6), both of which may play an important role in the development of distant metastases because of their adherent properties. Owing to their predominantly membranous localisation, they are also considered to have certain therapeutic potential. Apart from expression data obtained in the primary tumour, data for gene and protein expression patterns in distant breast cancer metastases are rare. Therefore this study focuses on analysing the distribution of ALCAM and CEACAM6 protein expression in breast cancer metastases from different sites.
Immunohistochemical staining for ALCAM and CEACAM6 in 117 breast cancer metastases derived from liver (n=24), lung (n=19), brain (n=21), bone (n=36) and skin (n=17) was performed.
Immunoreactive scores (IRS) for ALCAM in all metastases except skin metastases ranged from 2.63 to 5.10 (membranous) and 2.79 to 3.67 (cytoplasmic), showing a positive correlation with each other (r=0.690, p<0.001). In skin metastases, ALCAM expression was significantly stronger (membranous IRS, 8.76; cytoplasmic IRS, 7.12; p<0.001). Mean staining intensity for CEACAM6 was IRS 3.88. No or weak CEACAM6 and ALCAM staining (IRS 0-3) was seen in 53% vs 27% of all metastases.
Compared with CEACAM6, ALCAM showed significantly stronger protein expression in breast cancer skin metastases compared with metastases in all other sites.
为了预测和理解器官特异性转移的潜在机制,在原发性乳腺癌中已经确定了各种基因和蛋白质表达特征。这些表达特征通常包括几个编码黏附分子的基因,如活化白细胞细胞黏附分子(ALCAM/CD166)和癌胚抗原相关细胞黏附分子 6(CEACAM6),它们都可能由于其黏附特性而在远处转移的发展中发挥重要作用。由于它们主要定位于膜上,因此它们也被认为具有一定的治疗潜力。除了在原发性肿瘤中获得的表达数据外,关于远处乳腺癌转移中基因和蛋白质表达模式的数据很少。因此,本研究侧重于分析来自不同部位的乳腺癌转移中 ALCAM 和 CEACAM6 蛋白表达的分布。
对来自肝脏(n=24)、肺(n=19)、脑(n=21)、骨(n=36)和皮肤(n=17)的 117 个乳腺癌转移进行 ALCAM 和 CEACAM6 的免疫组织化学染色。
除皮肤转移外,所有转移中 ALCAM 的免疫反应评分(IRS)均为 2.63-5.10(膜)和 2.79-3.67(细胞质),彼此呈正相关(r=0.690,p<0.001)。在皮肤转移中,ALCAM 表达明显更强(膜 IRS,8.76;细胞质 IRS,7.12;p<0.001)。CEACAM6 的平均染色强度为 IRS 3.88。在所有转移中,53%的转移无或弱 CEACAM6 和 ALCAM 染色(IRS 0-3),而在所有其他转移中,这一比例为 27%。
与 CEACAM6 相比,ALCAM 在乳腺癌皮肤转移中比在所有其他部位的转移中表现出更强的蛋白质表达。