Original contributionOverexpression of phosphoprotein phosphatase 2A predicts worse prognosis in patients with breast cancer: a 15-year follow-up

•p-AKT was positively correlated with p-PP2A and Ki-67, but negatively correlated with HER2.•In TNBC patients, higher expression of p-PP2A correlates with poor clinical survival.•Targeting p-PP2A might be a promising strategy for treatment of breast cancer in the future.

SummaryBreast 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.