The impact of activated p-AKT expression on clinical outcomes in diffuse large B-cell lymphoma: a clinicopathological study of 262 cases
- Authors
- Hong, J. Y.; Hong, M. E.; Choi, M. K.; Kim, Y. S.; Chang, W.; Maeng, C. H.; Park, S.; Lee, S. J.; Do, I. -G.; Jo, J. -S.; Jung, S. H.; Kim, S. J.; Ko, Y. H.; Kim, W. S.
- Issue Date
- Jan-2014
- Publisher
- OXFORD UNIV PRESS
- Keywords
- diffuse large b-cell lymphoma; PI3K/AKT pathway; p-AKT
- Citation
- ANNALS OF ONCOLOGY, v.25, no.1, pp.182 - 188
- Journal Title
- ANNALS OF ONCOLOGY
- Volume
- 25
- Number
- 1
- Start Page
- 182
- End Page
- 188
- URI
- https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/12942
- DOI
- 10.1093/annonc/mdt530
- ISSN
- 0923-7534
- Abstract
- Background: Oncogenic phosphatidylinositol-3-kinase/serine-threonine kinase (PI3K/AKT) pathway plays a critical role in cell proliferation and growth. Phosphorylated AKT (p-AKT) has been reported to be abnormally overexpressed and to have poor prognostic impact in solid tumors. Patients and methods: To define the clinical implications of p-AKT expression in diffuse large B-cell lymphoma (DLBCL), we calculated arbitrary units (AUs) by multiplying the intensity and the proportion of p-AKT expression and investigated the impact of p-AKT expression on clinical outcomes. We assessed 262 patients with DLBCL. Based on a cutoff value of the upper limit of the third quartile of AUs, 56 patients were classified as high p-AKT and the remaining 206 patients were classified as low p-AKT. Results: The high p-AKT group was closely associated with more advanced stage (stage III-IV, P = 0.02), two or more extranodal involvement (P = 0.03), lactic dehydrogenase elevation (P = 0.03), higher International Prognostic Index risk groups (high intermediate/high, P = 0.02), and the presence of B-symptoms (P = 0.01). The high p-AKT group showed substantially worse overall survival (OS) (median OS, 115.0 months versus not reached, P = 0.004) and progression-free survival (PFS) (median PFS, 25.5 versus 105.8 months, P = 0.019) compared with the low p-AKT group. Multivariate analysis revealed that high p-AKT expression retained its significant poor prognostic impact for OS (hazard ratio 1.7; 95% confidence interval, 1.0-2.7; P = 0.031). The subgroup with high p-AKT expression and concurrent Epstein-Barr virus positivity showed worst prognosis with the median OS and PFS of 15.2 and 7.4 months. Conclusion: DLBCL patients with high p-AKT expression showed distinct clinical features and followed a more rapidly deteriorating clinical course with worse OS and PFS. Thus, a more effective treatment option should be developed for this subset of DLBCL patients, and targeting PI3K/AKT pathway may be a promising therapeutic strategy.
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