Downregulation of A20 Tumor Suppressor Gene Product in Classical Hodgkin Lymphomas and Subtypes of Non-Hodgkin Lymphomas.
Ali M Gabali, Farah Keyoumarsi, Thomas G Dafydd, Kojo Elenitoba-Johnson, Megan S Lim. The University of Michigan, Ann Arbor
Background: Nuclear factor-κB (NF-κB) is constitutively activated in many classical Hodgkin lymphomas (CHL) and non-Hodgkin lymphomas (NHL). A20 (TNFAIP-3) downregulates NF-κB through its dual ubiquitin-editing functions. A20 inactivating mutations/deletions have been demonstrated in CHL and many subtypes of NHL. This supports its role as a tumor suppressor gene in lymphoma. To date, however, little is known about the expression pattern and the localization of A20 protein in CHL and NHL. The objective of this study was to evaluate the expression of A20 in B-cell lymphomas and reactive lymphoid tissues.
Design: Tissue microarrays (TMA) were constructed from lymphomas (n=598) and reactive lymphoid tissues (n=49) from the archives of the Department of Pathology at the University of Michigan. A20 expression was evaluated by immunohistochemical analysis using the anti-A20 monoclonal antibody (diluted 1:250, clone EPR2663, EPITOMICS, CA). A20 expression was scored as positive if more than 25% of neoplastic cells showed immunoreactivity.
Results: In reactive lymphoid tissues, A20 was predominantly expressed in the nuclei of centroblasts and a subset of centrocytes within germinal centers. Interfollicular T-cells and mantle zone B-cells demonstrated weak nuclear expression of A20. Weak cytoplasmic expression was noted in histiocytes. Interestingly, a small number of DLBCLs showed weak nuclear expression of A20 and the rest were negative. In the negative cases, non-neoplastic small (B and T) lymphocytes served as internal controls and demonstrated weak nuclear expression of A20. The majority of MCLs and FLs demonstrated weak nuclear expression of A20, while approximately 37% of CLL/SLLs showed weak nuclear expression of A20. The difference in A20 expression between DLBCL and FL, and also between DLBCL and MCL, was statistically significant (P<0.05). Only 6% of the CHL cases expressed cytoplasmic A20. Prevalence of A20 expression was significantly lower in CHL in comparison to NHL (P<0.05). The results of our studies are tabulated below:
|Diagnosis||No. of cases||No. of positive cases||Staining pattern in neoplastic cells|