Clinicopathological and prognostic significance of phosphorylated PRAS40 (Thr246) in breast cancer

Background: Phosphorylation of proline-rich Akt substrate of 40 kilodaltons at Thr246 (p-PRAS40^Thr246) is a novel identified specific and stable biomarker for predicting phosphatidylinositol 3-kinase (PI3K) pathway activation and AKT inhibitor sensitivity.

Objectives: We investigated the expression of p-PRAS40^Thr246 in breast cancer, and their clinicopathological characteristics and prognostic significance.

Methods: The expression of p-PRAS40^Thr246 was detected by immunohistochemistry in 117 invasive breast cancer tumors.

Results: p-PRAS40^Thr246 was positive in 62 (53.0%) of 117 patients. p-PRAS40^Thr246 expression was significantly associated with late tumor stages and shorter survival, but not with other clincopathological characteristics. Furthermore, p-PRAS40^Thr246 was also an independent prognostic factor for invasive breast cancers.

Conclusion: High prevalence of p-PRAS40^Thr246 overexpression and its clinical significance in breast cancer suggests that this subgroup might benefit from PI3K inhibitors. We proposed that the detection of p-PRAS40Thr246 in breast cancer tissues should be included in the future clinical practice to develop patient-tailored treatments.