Chen Po-Ming, Chu Pei-Yi, Tung Shiao-Lin, Liu Chun-Yu, Tsai Yi-Fang, Lin Yen-Shu, Wang Wan-Lun, Wang Yu-Ling, Lien Pei-Ju, Chao Ta-Chung, Tseng Ling-Ming
Biobank, Chang Bing Show Chwan Memorial Hospital, Changhua 505, Taiwan.
Department of Pathology, Show Chwan Memorial Hospital, Changhua City 500, Taiwan; School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei City 24205, Taiwan; National Institute of Cancer Research, National Health Research Institutes, Tainan 701, Taiwan.
Hum Pathol. 2017 Aug;66:93-100. doi: 10.1016/j.humpath.2017.06.001. Epub 2017 Jun 9.
Breast cancer subtypes can be stratified by IHC expression of estrogen receptor, progesterone receptor, and human epidermal growth factor 2 (HER2). The signaling pathways mediated by these receptors are the dominant drivers of cell proliferation and survival in most human breast cancers. One of the most frequently overactivated pathways in breast cancer is the AKT signaling cascade. Protein phosphatase 2A (PP2A) acts as a switch to turn off signal transduction in the AKT pathway; however, it is frequently inactivated in many cancers by phosphorylation of Tyr-307 to form phosphoprotein phosphatase 2A (p-PP2A). This study aimed to investigate the clinical significance of p-PP2A and phospho-AKT (p-AKT) expression in 672 patients with breast cancer during a 15-year follow-up. The breast tissue microarray was evaluated for p-PP2A and p-AKT expression using IHC staining and scores. Analysis of IHC staining results revealed that p-PP2A expression was positively correlated with HER2, Ki-67, and p-AKT overexpression (P<.001, P=.003, and P=.001, respectively). At the time of diagnosis, breast cancer patients with higher p-PP2A expression had significantly shorter 15-year OS than patients with lower p-PP2A expression did (P=.017). Multivariate Cox regression analysis revealed that high p-PP2A expression was an independent prognostic factor for shorter OS (hazard ratio, 1.741; P=.012). Our data revealed that high p-PP2A expression is positively associated with HER2, Ki-67, and p-AKT expression. High p-PP2A expression correlates with poor clinical outcomes in breast cancer, especially in patients with TNBC.
乳腺癌亚型可通过雌激素受体、孕激素受体和人表皮生长因子2（HER2）的免疫组化表达进行分层。这些受体介导的信号通路是大多数人类乳腺癌细胞增殖和存活的主要驱动因素。乳腺癌中最常过度激活的通路之一是AKT信号级联反应。蛋白磷酸酶2A（PP2A）作为关闭AKT通路信号转导的开关；然而，在许多癌症中，它经常通过酪氨酸-307磷酸化而失活，形成磷酸化蛋白磷酸酶2A（p-PP2A）。本研究旨在调查672例乳腺癌患者在15年随访期间p-PP2A和磷酸化AKT（p-AKT）表达的临床意义。使用免疫组化染色和评分对乳腺组织芯片进行p-PP2A和p-AKT表达评估。免疫组化染色结果分析显示，p-PP2A表达与HER2、Ki-67和p-AKT过表达呈正相关（分别为P<0.001、P=0.003和P=0.001）。在诊断时，p-PP2A表达较高的乳腺癌患者的15年总生存期明显短于p-PP2A表达较低的患者（P=0.017）。多变量Cox回归分析显示，高p-PP2A表达是总生存期较短的独立预后因素（风险比，1.741；P=0.012）。我们的数据显示，高p-PP2A表达与HER2、Ki-67和p-AKT表达呈正相关。高p-PP2A表达与乳腺癌尤其是三阴性乳腺癌患者的不良临床结局相关。
