PTEN and p27 expression in mature T-cell and NK-cell neoplasms
Ayşegül H Uner1, Arzu Sağlam, Unsal Han
1Department of Pathology, Hacettepe University Medical Faculty, Sihhiye, Ankara, Turkey. unera@hacettepe.edu.tr
Abstract:
PTEN is a tumor suppressor gene located on chromosome 10q23 and is amongst the most commonly mutated genes in human cancers. The lipid phosphatase activity of Pten enables it to dephosphorylate PIP3, thereby antagonizing growth factor stimulated PI3-kinase signaling mediated by AKT/PKB. The growth inhibition effect of PTEN has been shown to be mediated by p27 which is one of the important effector molecules downstream of the AKT pathway. Recently the importance of the Pten and AKT pathway in the regulation of the immune system and development of hematological malignancies has been shown. Loss of Pten and p27 expressions were examined immunohistochemically in 45 patients with peripheral T- and NK-cell lymphoma. Partial or complete loss of Pten was detected in 66.7% of the cases of anaplastic large cell lymphoma (ALCL) compared to only 12.5% of all other mature T-/NK-cell lymphomas combined. Loss of p27 was identified in 64.9% of cases, which showed a positive correlation with Pten loss. In this study, we showed that loss of Pten is more frequent in ALCL as compared to other mature T-/NK-cell lymphomas, which strongly correlates with the loss of p27 expression. Our findings provide further evidence for the importance of the deregulation of the PI3K-AKT pathway in ALCL.
Insights
Loss of the PTEN tumor suppressor gene and its downstream effector p27 is frequent in anaplastic large cell lymphoma (ALCL). This PTEN/AKT pathway deregulation is more common in ALCL than other T-/NK-cell lymphomas.
Area of Science:
- Oncology
- Molecular Biology
- Immunology
Background:
- PTEN is a critical tumor suppressor gene regulating the PI3K-AKT pathway.
- The PI3K-AKT pathway, involving PTEN and its effectors like p27, plays a role in immune system regulation and hematological malignancies.
- Deregulation of this pathway is implicated in various cancers.
Purpose of the Study:
- To investigate the expression of PTEN and p27 in peripheral T- and NK-cell lymphomas.
- To determine the frequency of PTEN and p27 loss in anaplastic large cell lymphoma (ALCL) compared to other mature T-/NK-cell lymphomas.
- To explore the correlation between PTEN loss and p27 expression in these lymphomas.
Main Methods:
- Immunohistochemical examination of PTEN and p27 expression.
- Analysis of 45 patient samples with peripheral T- and NK-cell lymphoma.
- Comparative analysis of expression loss between ALCL and other mature T-/NK-cell lymphomas.
Main Results:
- Partial or complete loss of PTEN was observed in 66.7% of ALCL cases.
- PTEN loss was significantly more frequent in ALCL (66.7%) compared to other mature T-/NK-cell lymphomas (12.5%).
- Loss of p27 expression was identified in 64.9% of cases and showed a positive correlation with PTEN loss.
Conclusions:
- Loss of PTEN is a frequent event in ALCL, distinguishing it from other mature T-/NK-cell lymphomas.
- The observed loss of PTEN strongly correlates with the loss of p27 expression in ALCL.
- These findings reinforce the significance of PI3K-AKT pathway deregulation in the pathogenesis of ALCL.
