Foxp3 Is Differentially Expressed in Morphological Variants of US/Caribbean Adult T-Cell Leukemia/Lymphoma
Jinjuan Yao, Susan RS Gottesman, Albert Braverman, Constantine A Axiotis. SUNY Downstate Medical Center, Brooklyn, NY; Kings County Hospital Center, Brooklyn, NY
Background: Foxp3, a forkhead transcription factor of CD4+CD25+T regulatory cells (Treg), expression occurs in 36-68% of Japanese Adult T- cell leukemia/lymphoma (ATLL) patients. Foxp3 expression may only be seen in some tumor cells within same ATLL cases. Whether the heterogeneous expression correlates with morphological variants is not known. Foxp3+ Treg cells can become Foxp3- but this transition has not been described in neoplastic Treg cells.
Design: We identified 42 US/Caribbean ATLL patients from 1997-2011, for whom clinical information and biopsy specimens were available. All cases were classified morphologically, and diagnosed as ATLL on the basis of the Shimoyama criteria for clinical and laboratory findings. Immunohistochemistry for CD4, CD25, CD30 and Foxp3 was performed. We used a Foxp3 antibody (clone 221D/D3) which recognizes only Foxp3 and does not cross react with other Foxp proteins. Foxp3 status in the pleomorphic small, medium, large cell types, and anaplastic variants was compared using the chi-square test. Foxp3 expression in biopsies obtained at different times from 16 patients was also compared.
Results: Foxp3 was expressed in the majority of lymphoma nuclei in 26/42 cases (58 biopsies) of ATLL (61.9%). All cases were positive for CD4 and CD25. Foxp3 and CD25 intensities were correlated and varied amongst morphological types, and amongst nodal regions. Foxp3 was positive in all 13 pleomorphic small, 11/14 (79%) medium, 10/23 (44%) large, but negative in all 8 anaplastic variants. Differences were significant between the pleomorphic small versus large (p= 0. 0024), pleomorphic small versus anaplastic (p=0. 0001), and medium versus anaplastic variants (p=0. 0019). All 8 CD30+biopsies were Foxp3-. Two patients with initial CD30-Foxp3+pleomorphic medium were CD30+anaplastic with negative Foxp3 10 and 72 months later. A third patient remained CD30-, but morphologically transformed to large cell, with conversion from Foxp3+to Foxp3-. Sequential biopsies from 13/16 patients revealed no change in morphology or Foxp3 expression.
Conclusions: In our study Foxp3 expression is prevalent in the pleomorphic small and medium, less so in large cell, and absent in anaplastic variant. Foxp3 is often lost during the large or anaplastic transformation. The clinical significance of this phenomenon warrants further investigation.
Wednesday, March 21, 2012 9:30 AM
Poster Session V # 192, Wednesday Morning