FOXP3 Expression in Diverse T-Cell Lymphomas.

BACKGROUND: Foxp3 is a key regulatory gene required for the development and function of:

1. regulatory CD4⁺CD25^high T cells (T_reg) specialized in maintaining the balance between immunity and tolerance and

2. activated conventional CD4⁺CD25^low T cells without suppressive activity.

Until now it is not yet possible to study human FOXP3+ T_reg irrespective of their CD25 expression. Previous studies had reported FOXP3+ T cells in Adult T-cell Leukemia/Lymphoma cells (ATLL) related to HTLV-1 and in other lymphomas types the FOXP3 expression was only detected in the reactive T-cell background.

AIM: To determine the specifity and prognostic value of the FOXP3 expression in T-cell lymphomas.

METHODS: A retrospective study was performed on 46 samples collected from diverse T-cell lymphomas in our institution. A highly sensitive immunohistochemical method was used to demonstrate FOXP3 protein expression with a mouse monoclonal antibody (clone 236A/E7ABCAM) in most formalin-fixed paraffin-embedded tissue sections from lymph nodes, skin, bone marrow and extranodal sites samples as cavum and stomach. We did not co-stained with CD25 and considered a FOXP3+ tissue when positivity was > 80% of toumor cells. Correlation with survival was done.

RESULTS: Among the 46 evaluable T-cell lymphomas collected, 33 were ATLL, 7 mycosis fungoids (MF) and 6 unspecified peripheral T-cell lymphomas (U-PTCL). Among the 33 ATLL: lymphomatous=17, acute=11, smoldering=1, chronic=1, cutaneous=1 and undefined=2. FOXP3 expression in tumour cells was detected in 24% (8/33) of ATLL cases, was negative in MF tumour cells and detected in 33% (2/6) of U-PTCL. Interestingly FOXP3 expression between 30–40% was expressed in 3 MF cases associated to T_reg cells. Among the ATLL cases FOXP3 positivity were obtained in 35% (6/17) of lymphomatous type; 18% (2/11) of acute ones and none in others ATLL types studied. We failed to demonstrated any correlation between FOXP3 status and survival.

CONCLUSIONS: FOXP3 is expressed in ATLL and T-cells peripheral lymphoma. T_reg presence in the tumour environment plays an important immune system response role and its identification should be fundamental.