The Clinical Significance Of Activated p-AKT Expression In Peripheral T-Cell Lymphomas

The oncogenic phosphatidylinositol-3-kinase/serine-threonine kinase (PI3K/AKT) pathway mediates diverse prosurvival signals and promotes the malignant phenotype of cancer cells through multiple downstream pathways. We aimed to define the prognostic role and clinical significance of p-AKT expression in peripheral T-cell lymphomas (PTCLs).

We evaluated the p-Akt expression in patients with PTCLs using tissue microarray(TMA) technology. The intensity of p-AKT staining was scored as 0, 1, 2, and 3 and the proportion of p-AKT positive cells was scored from 0% to 100%. p-AKT expression score was expressed as arbitrary units (AUs), calculated by multiplying the intensity score by the proportion score.

A total of 63 PTCL patients were analyzed (PTCL not otherwise specified [PTCL-NOS, n=16], angioimmunoblastic T-cell lymphoma [AITL, n=19], and anaplastic large cell lymphoma [ALCL, n=11] and natural killer T-cell lymphoma [NKTCL, n=17]). The upper limit of the third quartile (Q3) of the AU values was 120. High p-AKT group (AU>Q3) included a higher proportion of NKTCL (41.7%) and ALCL (33.3%) subtypes, while low p-AKT group (AU≤Q3) included higher proportion of AITL (37.3%) and PTCL-NOS (25.0%) subtypes. High p-AKT group showed substantially poorer overall survival (OS) (median OS, 2.3 months vs. 25.2 months, P< 0.001) compared with the low p-AKT group. Multivariate analysis showed that high p-AKT group retained its significance as an independent prognostic factor for poor OS (hazard ratio [HR] 6.5; 95% confidence interval [CI], 2.7 – 15.9; P< 0.001) and poor PFS (HR 4.7, 95% CI; 2.1 – 10.6, P< 0.001).< 0.001) compared with the low p-AKT group.

PTCLs having high p-AKT expression showed a significantly worse survival than patients with low p-AKT expression. Thus, more effective treatment approaches are needed for this subset of patients with PTCLs, and we suggest inhibition of PI3K/AKT pathway may be a promising therapeutic strategy in PTCLs.

No relevant conflicts of interest to declare.