Ihnen M, Müller V, Wirtz R M, Schröder C, Krenkel S, Witzel I, Lisboa B W, Jänicke F, Milde-Langosch K
Department of Gynecology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Breast Cancer Res Treat. 2008 Dec;112(3):419-27. doi: 10.1007/s10549-007-9879-y. Epub 2008 Jan 3.
Activated Leukocyte Cell Adhesion Molecule (ALCAM, also called CD 166, MEMD) as cell surface immunoglobulin is reported as prognostic marker in breast cancer, but its predictive value has not yet been evaluated. We have analyzed ALCAM protein expression by Western Blot analysis (n = 160) and mRNA expression by cDNA microarray analysis (n = 162) in primary mammary carcinomas. Both expression results were obtained in 133 cases, showing a strong positive correlation between protein expression and mRNA expression (P < 0.001). Neither ALCAM protein nor mRNA expression are correlated to histological type, grading, stage or age of patient. However, ALCAM protein expression correlates positively with estrogen receptor status (ER) (P = 0.025). A stratified subgroup analysis showed positive correlation of high ALCAM mRNA expression with longer overall survival (OAS; P = 0.0012) in patients treated with adjuvant chemotherapy (n = 100). In contrast, patients with high ALCAM mRNA expression who did not receive chemotherapy tended to have a worse prognosis. Similar but weaker correlations were found regarding ALCAM protein expression data. The predictive impact of ALCAM mRNA expression in chemotherapy treated patients was corroborated by multivariate Cox regression analysis also including histopathological markers (P = 0.001 for OAS). Our overall results reveal that high ALCAM expression levels in primary tumors might be a suitable marker for prediction of the response to adjuvant chemotherapy in breast cancer.
活化白细胞细胞黏附分子（ALCAM，也称为CD166、MEMD）作为一种细胞表面免疫球蛋白，据报道是乳腺癌的预后标志物，但其预测价值尚未得到评估。我们通过蛋白质印迹分析（n = 160）分析了原发性乳腺癌中ALCAM蛋白的表达，并通过cDNA微阵列分析（n = 162）分析了其mRNA表达。在133例病例中均获得了两种表达结果，显示蛋白表达与mRNA表达之间存在强正相关（P < 0.001）。ALCAM蛋白和mRNA表达均与组织学类型、分级、分期或患者年龄无关。然而，ALCAM蛋白表达与雌激素受体状态（ER）呈正相关（P = 0.025）。一项分层亚组分析显示，在接受辅助化疗的患者（n = 100）中，高ALCAM mRNA表达与较长的总生存期（OAS；P = 0.0012）呈正相关。相比之下，未接受化疗的高ALCAM mRNA表达患者预后往往较差。关于ALCAM蛋白表达数据也发现了类似但较弱的相关性。多变量Cox回归分析（也包括组织病理学标志物）证实了ALCAM mRNA表达在化疗患者中的预测作用（OAS的P = 0.001）。我们的总体结果表明，原发性肿瘤中高ALCAM表达水平可能是预测乳腺癌辅助化疗反应的合适标志物。
